Eberlé, F.

Gazin, Pierre

Hengy, C.

Mulder, L.

Horizon / Pleins textes

I N  V I V O  M O N I T O R I N G  O F  C H L O R O Q U I N E  
S E N S I T I V I T Y  O F  P L A S M O D I U M  F A L C I P A R U M  
I N  E D E A ,  S A N A G A  M A R I T I M E  D I S T R I C T ,  
S O U T H  W E S T  C A M E R O O N  
Mulder L.1, Eberlé F.2, Hengy C.2, Gazin P.2 
Summary 
The town of Edea is located in South West Cameroon in a zone of chloroquine resistance. 
Falciparum malaria is hyperendemic. We have performed an in vivo study of chloroquine sensitivity 
in 190 school children 6 to 12 years of age. In three days they are given 25 mg/kg chloroquine orally. 
Parasite densities are controlled on D3 and D7. 
123 children (64.5%) had positive blood films for malaria at DO. The splenic index was 27%. 
68 children met the enrollment criteria. Their GMPD was 1585 PRBC"m3. On D3, 16 children 
(23.5%) still carried parasites with a GMPD of 40, while on D7 12 children (17.5%) remained 
parasited with a GMPD of 141 PRBWmm3. Two of them had a relatively high parasitaemia. We 
conclude that chloroquine remains the drug to be used at first intent. 
Résumé 
ETUDE IN VIVODE LA SENSIBILITE A LA CHLOROQUINE DE PLASMODIUM 
FALCIPAR UM A EDEA, DEPARTEMENT DE LA SANAGA MARITIME, SUD-OUEST DU 
CAMEROUN 
La ville d'Edea est située au sud-ouest du Cameroun dans une zone où la chloroquinorésistance 
est connue depuis 1985. Le paludisme y est hyperendémique. En mai 1989, nous avons réalisé un test 
de sensibilité in vivo chez 190 écoliers âgés de 6 à 12 ans. Ils recoivent 25 mg/kg de chloroquine per 
os en 3 jours. Les densités parasitaires sont cóntrôlées à 53 et J7 sur goutte épaisse. 
123 enfants (64,5%) sont porteurs de parasites àJO. L'indice splénique est de 27%. 68 enfants 
sont inclus dans l'étude. Leur parasitémie moyenne initiale est de 1585 GRP/mm3. A 53, 16 d'entre 
eux (23,5%) sont porteurs d'hématozoaires à une densité moyenne de 40 GRP/mm3. A J7, 12 
(1 73%) ont encore des parasites, à une densité de 141 GRP/mm3. Deux individus ont une parasitémie 
relativement élévée. La chloroquine reste l'antimalarique à utiliser en première intention dans cette 
région. 
Introduction 
E W A B  May 1989 
'University of Nijmegen; The Netherlands and OCEAC PB 288 Yaoundé, Cameroon 
OCEAC, Yaoundé 
8.09.89 
World areas with chloroquine resistant falciparum malaria are progressively spreading in Africa 
from East to West. In the South West of Cameroon chloroquine resistance is known since1985.( 12) 
Since then various studies have confirmed this situation (8) and assessed that chloroquine 
resistance is focussed on three main areas in Cameroon: the coast at Limbe (l), at Kribi (7) and in the 
city of Yaoundé.(4) 
Edea is situated on the banks of the river Sanaga in a tropical rain forest zone. Edea is the chief 
town of the Sanaga Maritime district with one of the most important industrial centers of Cameroon, 
the aluminum factory ALUCAM. Malaria is considered to be hyperendemic in this area. (6) 
Although situated in the center of the principal zone of chloroquine resistance Edea has never 
been the subject of a study to chloroquine sensitivity. Macaigne et al have studied amodiaquine in 
ALUCAM children and found good effectiviness.(9) We decided to carry out a study in Edea because 
of massive chloroquine administration, particularly (free of charge) under ALUCAM employees and 
their families and the fact that medical centers report an increasing number of consultations and 
hospitalizations for malaria since 1986. 
. 
Materials and methods 
The quarter Pongo can be regarded as representative for the town of Edea. There are two primary 
schools of which the catholic Saint Martin school has 664 pupils divided over 1 1 classes. Four classes 
with about 200 pupils in the age range between 6 and 12 years have been studied. 
In hyperendemic areas of Africa 30 days follow-up cannot be achieved without exposure to 
reinoculation by sporozoites. In May 1989 we carried out the simplified in vivo test over 7 days 
according to the method given by the OCEAC. ( 5 )  
All pupils present at the first day of the study (DO) were examined on spleen rate, weight and 
fever. We interrogated wether the children had access to the free medical service of ALUCAM. Blood 
was taken for thin and thick smears. 
Detection of parasites was done on thick smear. The identification of Plasmodium species was 
done on thin smear. The parasite density was established by counting 30 fields (about 600 leucocytes) 
of the thick smear and/or by counting 100 fields (about 20.000 erythrocytes) on the thin blood film. 
The density was determined on the base of 8000 leucocytes and 4 million erythrocytes per mm3 of 
blood volume. 
All children were given 10 mgkg of chloroquine per os on DO, the same dose on D 1 and a dose 
of 5 mgkg on D2 resulting in a total dose of 25 mgkg in three days. Administration was done under 
supervision of intake until at least 15 minutes afterwards. Parasite density was controlled at D3 and D7 
by thick smear. 
Results 
190 children were screened. Their mean age was 9 years with a mean weight of 26 kg. 5 
60 children had access to the ALUCAM medical service. 
children had fever on DO. 
8.09.89 2 
Parasitological findings 
123 children (64.5%) had positive blood films for malaria. In 98% of the cases, P. iàlcipamm 
The geometric mean parasite density (GMPD) in subjects with parasites was 525 PRBC/mm3 
without age variation. The gametocyte index of P. filcipamm, 3.5%, was low. The splenic index was 
27%. There was a significant negative correlation between age and spleen size (r= 0.16, p < 0.05). 
Average enlarged spleen according to Hackett (3) was 1.64 (S.D. 0.72). 
was present. P. malilljae was seen in 6.5% of the cases and P. ovale in 1%. 
There is a positive correlation between spleen size and parasite density (r = 0.19, p < 0.05). 
There was a slight difference in spleen rate between the ALUCAM and non-ALUCAM group (Table 
1). 
Of the investigated children 1.5 % were carrier of microfilaires of Mansonella perstans. One 
child had microfilaires of Loa loa. 
Effectiveness of chloroquine 
The subjects allowed in the sensitivity test were those with a parasitaemia on DO exclusively of 
P. fdcipmm with parasite counts of at least 500 trophozoitedmm3 which have completed their 3 days 
treatment on DO, D1, D2, or D3. We didn't observe complaints of pruritis. Only one child was 
dropped from the study on D 1 for excessive vomiting at the time of the treatment. 68 children met the 
enrollment criteria; their mean age, 9 years, and mean weight, 26 kg, being not different of the whole 
group. Their geometric mean parasite density (GMPD) was of 1585 PRBC/mm3 * 
On D3 16 children (23.5%) still carried parasites with a GMPD of 40, while on D7 12 children 
(17.5%) remained parasited with a GMPD of 141. These didn't differ from the whole group in age nor 
weight. Their initial parasite density was the same of those included in the test. 
Two subjects, both from the non-ALUCAM group, showed a persistant parasitaemia (table 2). 
Remarkably there is no parasitological difference found between the ALUCAM and non- 
ALUCAM children included in the test (table 3). 
Discussion 
The spleen rate (26%) differs very significantly from the one observed in a neighbouring rural 
community (p < 0,001).(2) The slight difference in the spleen rate between ALUCAM and non 
ALUCAM children indicates a trend that antimalarial drugs are most frequently being used in the first 
group. The high parasite rate is classic for Central Africa. (10,13) There are no remarkable age or 
quarter differences. 
Chloroquine is used at a dose of 25 mgkg per os in three days. The intake of tablets is 
supervised. Chloroquine blood and/or urine level are not controlled, thus it remains impossible to 
confirm that all children had a sufficiently high chloroquine blood level (> 65 nmov1). (1 1) 
In 68 children admitted to the study, 12 (17.5%) have demonstrated in vivo parasitological 
resistance mostly at a low level. Four of them have early RI resistance and seven a typical RI1 
resistance. 
In the case of the child who had fever on DO and a parasitaemia of 10,000 PRBC/mm3, we 
observe a lack of effectiveness of the chloroquine which requires an alternative treatment. 
8.09.89 3 
Conclusion 
The in vivo 7 days test performed in a small town in Southwest Cameroon shows that in May 
1989 chloroquine is still effective in a great majority of school children. Chloroquine remains the 
treatment of first intent in case of malaria in this area. 
References 
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High level of sensitivity to chloroquine of 72 
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7 16 
(2) Gazin P.; Le Goff G.; Ambassa P.; Mulder 
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[ ] Publication in French 
SUppl. 2: 26-33 
8.09.89 4 
Table 1: Malarial indices of Alucam and non-Alucam children in May 1989 before 
antimalarial treatment 
Age Sex Weight DO (***) D3 
7 F 19 750 110 
8 F 20 10000 350 
Alucam 
number (n=) 60 
parasite rate 62% 
part of P. ovale or 
P. malariae in infections 3.3% 
GMPD * 447 
spleen rate 22% 
ms ** 1.46 (SD 0.66) 
D7 remarks 
1000 GametesD3 
8000 Fever Dl  
Non Alucam 
130 
66% 
5.5% 
501 
29% 
1.70 (SD 0.74) 
Table 2: Characteristics of 2 children with low in vivo response of Plasmodium 
faleipa" to chloroquine 
Table 3: Prevalence and geometric mean parasite density of children included in the 
in vivo chloroquine test 
Alucam 
nonAlucam 
Alucam 
nonAlucam 
Parasite rate 
GMPD (*) 
DO 
n=21 
n=49 
1445 
1660 
D3 
24% 
22% 
26 
50 
D7 
19% 
16% 
76 
190 
* Geometric Mean Parasite Density expressed in parasited red blood cells /mm3 
of blood volume 
** Average Enlarged Spleen according to Hackett 1 
*** Parasite density on day O, day 3 and day 7 
8.09.89 5 


In vivo monitoring of chloroquine sensitivity of Plasmodium falciparum in Edea, Sanaga maritime district, South West Cameroon

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