BRIEF COMMUNICATIONS
Prophylaxis Failure Against Vivax Malaria in Guyana, South
America
Janice I? Barrett and Ronald H . Behrens
Chloroquine-resistant Plasmodium vivax was originally reported in Papua, New Guinea by Reickman in
1989.' In the same year, in Colombia, South America,
Arias and Corredo? reported relapses of 11 patients suffering from vivax malaria, following a chloroquineprimaquine regimen. Garavelli and Corti3 suggested
chloroquine-resistant Plusmodium vivux may be present
in Brazil following these therapeutic relapses. Further therapeutic failures in returned travelers from South Anierica were reported by Moore et a1 (1994).4We report vivax
malaria in a group of expeditioners visiting Guyana
who, whereas compliant with antimalarial chemoprophylaxis, developed clinical malaria, adding evidence to
the presence of chloroquine-resistant Plasmodium vivux
in South America.
Raleigh International is a youth development charity that undertakes environmental and community projects around the world. These are usually in remote
locations. Nine expeditions in countries such as Chile,
Belize, Zimbabwe, Uganda, and Malaysia are organized
annually. A project manager and a medical officer are
placed at each site, along with approximately 10 venturers
(age 17-25.) Participants are of all nationalities,but, at present, they are predominantly British.
which utilized postal questionnaires, was undertaken
to examine the use of malaria prophylaxis and to detail
episodes of malaria in members of the expeditions.
Two hundred questionnaires were sent out 6 months
after the first expedltion, and 3 months after the second expedition.The infornution collected covered the following:
1. Project sites visited (i.e., area).
2. Chemoprophylaxis used, and doses missed during and
after exposure. Antimosquito measures used.
3. Use of limb-covering measures at high-risk periods
4. Use of treated and untreated nets (impregnated
with permethrin).
5. Use of insect repellents.
6. Detailing of any malaria episodes.
Results
One hundred and eight questionnaires were returned
(54%)).
Participants were split equally between males and
females. Chemoprophylaxis, chloroquine and proguanil,
was used by all participants with good (no missed doses)
compliance in 59%;poor (missing one weekly or two daily
doses throughout) compliance in 23%; and noncompliance by the remainder (Fig. l).All mosquito nets were
impregnated with permethrin on arrival in the country;
85% of respondents slept under a net (8%relied on nets
alone, and the remainder lived in screened acconimodation and used nets). Data on other antimalarial measures revealed a high degree of compliance.
Chloroquine and proguanil chemoprophylaxis was
reported complete (no missed doses) until diagnosis of
10 cases of vivux malaria was reported. Two patients
reported missing two or fewer doses of chloroquine,
and the remaining two patients missed more than two
chloroquine doses during the period of chemoprophylaxis use. All reported using antimosquito measures.The
clinical diagnoses of vivax malaria was made by the expedition physicians and was microscopically confirmed by
regional laboratories in Letham or Georgetown. In two
cases diagnosis was made in U.K. hospital laboratories,
where the individuals first presented.Treatment was with
Method
From July to December 1993, Raleigh ran two
consecutive expeditions to Guyana, South America. Over
200 participants were involved in projects in 15 locations.
Medical officers diagnosed a significant increase in cases
of vivax malaria, and as a consequence,a retrospectivestudy,
Janice t? Barrett, BSc, RN, and Ronald H. Behrens MD,
MRCP: Raleigh International, London, U.K. and Hospital
for Tropical Diseases Travel Clinic, London, U.K.
Reprint requests: Ron H. Behrens, Hospital for Tropical
Diseases Travel Clinic, 4 St. Pancras Way, London, U.K.
NW1 OPE.
J Travel Med 1996; 3:60-61.
60
Barrett and Behrens, Prophylaxis Failure Against Vivax Malaria i n Guyana, S o u t h America
BOX
50%
Expedition 1
Expedition 2
1
4D%
30%
s
20%
10%
0%
T-
Good
compllsnce
Poor
compliance
1
7-
No
compliance
Malaria
Cases
Figure 1 Compliance practice in participants of t w o expeditions and the proportion of vivax malaria in respondents.
Reported compliance of respondents t o antimalarial drug use
by members of the two expeditions to Guyana 1993 and proportion of cases of vivax malaria in the two expeditions. Good
compliance = no missed doses; poor compliance = t w o or
fewer doses missed throughout use; no compliance = more than
t w o doses missed throughout use.
chloroquine and primaquine in eight; chloroquine and
quinine alone in two; and various other regimens in the
remainder. Two subjects relapsed, after return to the
U.K., with microscopically confirmed vivux malaria,
which was successfully retreated with cloroquine and primaquine.
Discussion
The World Health Organization (WHO) defines
drug resistance as the ability of a parasite strain to survive and/or multiply, despite the administration and
absorption of a drug given in doses equal to, or higher
than, those usually recommended by W H O in 1973.5The
chemoprophylaxis doses used may not be covered by this
definition, but as infection in the presence of adequate
blood levels of chloroquine occurred in 71% of cases, there
appears to have been a parasite with reduced sensitivity
to chloroquine.
Arias first reported 11 vivux relapses 49-166 days after
chloroquine and primaquine treatment and subsequent
nonexposure.2 The long delay to relapse suggests these
are not recrudescences consequent to chloroquine resistance, but failure of primaquine to elininate the liver
stages. Garavelli and Corti3 also report Plasmodium vivux
resistant to chloroquine following treatment failure in
61
Brazil. Others dispute those interpretations, putting the
apparent resistance down to a relapse of the original
infection.",' In discussion it was agreed that primaquine
resistance is well recognized, but no agreement whether
or not the parasite was resistant to chloroquine and to
the presence of chloroquine-resistant strains in South
America was reached.
Reported compliance with antimosquito measures
and chemoprophylaxis was high, but the potential for mireporting of prophylaxis use must be recognized.The presence of a medlcal officer on each site provided supervision
and reinforcement of the use of preventative measures.
The correlation between reported compliance and blood
levels in a similar group of venturers visiting Zimbabwe
showed that 15 of 16 had chloroquine levels consistent
with their reported use,* supporting the use of reported
drug compliance as a proxy of true use in this group of
travelers.
Geographically, the project sites that were visited were
located in the southwestern part of the country, and the
resistant species may be associated with this region.This
high breakthrough in nonimmune subjects using combined chloroquine and proguanil chemoprophylaxis suggests that Plasmodium vivux strains capable of surviving
and multiplying at normal prophylactic plasma drug levels are present in Southwest Guyana and that chloroquineresistant Plasmodium vivux may exist in South America.
Alternative prophylaxis regimens for chloroquine resistant Plusmodium vivux malaria have not been well investigated, and mefloquine has yet to be shown effective.
References
1. Reicknian KH, David DR, Hutton DC. Plasmudium uiuax
resistance to chloroquine? Lancet 1989; 1183.
2. Arias AE, Corredor A. Low response of Colombian strains
of Plasmodium viuax to classical antimalarial therapy. Trop
Med Parasitol 1989; 40:21-23.
3. Garavelli PL, Corti E. Chloroquine resistance in Plasmodium
uivax: the first case in Brazil.Trans Roy Soc Trop Med Hyg
1992; 863128.
4. MooreTA,TomaykoJF Jr,Wierman AM,Rensimer E R , m t e
AC Jr. Imported malaria in the 1990s: a report of 59 cases h n i
Houston,Texas. Arch Family Med 1994; 3:130-136.
5. World Health Organization. Resistance of malaria parasites
to drugs:WHO technical report series 1965; 296:lO.
6. Loyola EG, Rodriguez M H . Chloroquine-resistant Plasmudium uiuax in Brazil! Trans Roy Soc Trop Med Hyg 1992;
86:570.
7. Canessa A, Mazzarello G, Cruciani M , Bassetti D. Chloroquine
resistant vivax in Brazil.Tran5 Roy SocTrop Med Hyg 1992;
86:570.
8. Behrens R H , Pryce DI. Prophylaxis compliance in patients
with travellers malaria. Proceedings of theThird Conference
on International Travel Medicine, Paris, France,April 26-29,
1993:123.