Rogier, C.

Trape, Jean-François

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TRANSACTIONS F THE ROYAL S o a m  OF TROPICAL MEDICINE AND HYGIENE (1993) 87, 245-246 
M "3 
245 
Malaria attacks in children exposed to high transmission: who is protected? 
~~ 
Christophe Rogier' and Jean-François Trape2 
2Laboratoire de Paludologie, ORSTOM, B.P. 1386, Dakar, Sénégal 
'Service d'EpidÉmwlogie, Institut Pasteur, B.P. 220, Dakar, Sénégal; 
b Abstract 
In persons naturally exposed to high transmission, how significant, in terms of immune protection, is the 
occurrence or non-occurrence of a malaria attack during a given observation period? This question was stu- 
died in a West African village where Plasmodium falciparum malaria is holoendemic with intense and peren- 
nial transmission. A cohort of 94 children aged 4 months14 years from Dielmo village, Sénégal, was 
studied over 4 months, June-September 1990. 41 children had no malaria attack and 53 children suffered 
between one and 6 attacks. The average number of attacks was 1.80,2.25, 1.87,0.29 and 0.07, respectively, 
in children aged 4-11 months, 1-2,3-6,7-10 and 11-14 years. The transmission level was 75 infective bites 
per person. Analysis of the distribution of the number of attacks in individual children suggested that all 
children within the same age group had either the same, or a very similar, level of protection. This suggests 
that the acquisition of clinical protection in areas where malaria is highly endemic involves a progressive and 
homogeneous decrease of the probability of having a malaria attack (attacks occur less frequently as age in- 
creases, in all children), rather than the acquisition of complete protection by an increasing number of child- 
ren. The differences between the number of clinical attacks observed in young children and their presumed 
exposure suggest that protective mechanisms become effective from the first reinfection onwards, and are 
independent of the cumulative exposure to a great variety of antigens. 
ria is highly endemic, epidemio- 
e consistently shown that mortality and 
morbidity due to malaria occur mainly among infants 
ànd'young children. In older children and adults, ac- 
quired immunity is usually sufficient to prevent tliè-de- 
velopment of symptoms during infections. The precise 
mechanisms of this protection are still unclear and a com- 
mon method of investigation is the comparison of the re- 
sults of immunological tests on persons considered to be 
either protected or unprotected. In order to constitute 
these 2 sample groups within a population living in an 
endemic area, 2 different criteria could be used: either 
the person's age (older children and adults are presumed 
to be protected), or the clinical data obtained from pros- 
pective surveillance (persons who have an attack during 
the observation period are presumed unprotected). Both 
methods present specific problems in the interpretation 
of the results. With the first method non-specific factors 
related to age may interfere with the results (BAIRD et al., 
1991); with the second, i,t is_ necessary to determine the 
significance, in terms of protection, of the occurrence or 
non-occurrence of a malaria attack during a given obser- 
vation period. We have studied this latter problem, using 
preliminarv observations carried out over a '4-month 
As part of a research 
lage in Sériéga! (population 255) has been the object of a 
longitudinal study since 1990, consisting of close moni- 
toring of numerous epideñiiologícal, clinical and immu- 
nological factors. Malaria transmission in this village is 
intense and perennial (1 15 infective bites per person per 
year in 1990) and the parasite rate is over 85% in children 
hroughout the year (TRAPE et al., 
In order to identify all malaria attacks, koutine medical 
examinations were carried out from 1 June to 30 Septem- 
ber 1990 (maximum transmission period) by a medical 
team operating day and night in the village. Households 
were visited daily. The systematic observations included 
thick blood film examinations twice a week and tempera- 
ture readings every 2 d. Supplementary thick smears, 
medical examinations, and further tests were made when 
fever or other symptoms were present. 
For this study, we took into account the results of 94 
children aged between 4 months and 14 years who had 
Address for correspondence: Dr J. F. Trape, ORSTOM, B.P. 
1386, Dakar, Sénégal. 
spent at least 75% of their life in Dielmo. We considered 
as Plasmodium falciparum attacks 120 episodes of fever 
(temperature 238-5"C) associated with sharp increases in 
parasitaemia (Trape et al., paper in preparation). During 
110 of the attacks (92%) the parasitelleucocyte ratio ex- 
ceeded 2, a criterion previously proposed for diagnosing 
clinical malaria among children living in holoendemic 
areas (TRAPE et al., 1985). With the exception of 29 brief 
attacks which were diagnosed retrospectively, all attacks 
were immediately treated using a 3 d regimen of 
quinine+quinidine+cinchonine (Quinimax@, 25 mg/kg/d) 
(DELORON et al., 1989). No severe attack was observed. 
The absence of chemoprophylaxis andor self treatment 
was controlled by systematic determination of antimala- 
rial drugs in the urine once a month, and during the 
course of all fever cases, using the modified Saker-Solo- 
mons test (MOUNT et al., 1989). P. falciparum was pres- 
ent in 85% of the thick blood films taken in the absence 
of fever. Trophozoites were observed in all except one 
child during the study. 
Results 
During the 4 months surveillance period, 41 children 
had no P. falciparum attack, and 53 children suffered be- 
tween one and 6 attacks. The maximum average number 
of attacks was among children aged 1-2 years, and it de- 
creased -with increasing age (Table l: p<O.OOO 
c 
I 
Age groupa children attacks per child 
4-11 months 5 9 1.80 
1-2 years 20 45 2.25 
3-6 years 31 58 1-87 
7-10 years 24 7 0.29 
11-14 years 14 1 0.07 
Total 94 120 1-28 
"Age at inclusion. 
with square root transformation). This decrease was par- 
ticularly obvious in children older than 6 years: the aver- 
age number of attacks was 6 times higher in children 
aged 3-6 years than in those aged 7-10 years. 
To determine whether the children who had no attack 
during the observation period could be considered to be 
better protected than the other children, we compared 
the observed distribution of children having had O, 1, 2, 
, 
i 
246 
3, 4 or more attacks with the expected Poisson distribu- 
tion, which would reflect a similar probability for all 
children of suffering an attack. Table 2 shows that the 
observed and expected numbers did not differ signifi- 
cantly when children aged 4 months-6 years and 7-14 
years were considered separately. In contrast, when all 
children were considered together, the observed and ex- 
pected figures were significantly different (P<O.OOl ;  x2 
test). 
Table 2. Observed and expected distribution of children according to 
age and the number of falciparum malaria attacks in individual 
children over a four-month period 
. Age group 
No. of 4112-6 years 7-14 years Total 
attacks 
O 11 7.6 30 30.7 41 26.2 
1 11 15.1 8 6.5 19 3 3 3  
Observed Expected Observed Expected Observed Expected 
2 12 15.1 O 0.7 12 21.4 
3 14 10.1 O 0.1 14 9.1 
< 8 8.1 O O 8 3.8 
Total 56 56 38 ' 38 94 94 
Discussion 
These observations are compatible with the assump- 
tion that all children within the same age group were 
equally protectedsusceptible. At a given age, all children 
in this survey had either the same level of protection 
(whether or not they suffered a malaria attack during the 
observation period), or a level of protection so similar 
that an observation period of 4 months, with this number 
of children, was insufficient to demonstrate differences 
between them. This suggests that the acquisition of clini- 
cal protection in areas where malaria is highly endemic 
involves a progressive and homogeneous decrease of the 
individual probability of having a malaria attack (attacks 
occur less frequently as age increases, in all children), 
rather than the àcquisition of complete protection by an 
increasing number of children. I f we had chosen to class 
children without malaria attacks in the protected group, 
and those children with malaria attacks in the unpro- 
tected group, 20% (11/56) of children aged between 4 
months and 6 years would have been counted as pro- 
tected, whereas the probability of their suffering an at- 
tack should be considered to be equal to that of other 
children in the same age group. Conversely, 21% (8/38) 
of children aged 7 to 14 years would have been counted 
among the unprotected children, whereas their level of 
protection should also be considered to be equal to that 
of other children in the same age group. 
Can the youngest children in this survey be considered 
as unprotected? The transmission level of malaria in 
Dielmo, during the 4 months observation period, was es- 
timated by night-time mosquito collection and dissection 
to be 75 infective bites per person (KONATE, 1991). The 
differences between the number of clinical attacks ob- 
served in young children and their presumed exposure 
seems to be much too high to be explained only by the 
fact that children were less exposed than adults to mos- 
quito bites (PORT er al., 1980), or by the failure of some 
infected mosquitoes to transmit sporozoites (ROSENBERG 
et al., 1990). Therefore, even in young children, it is 
probable that only a small proportion of infectitins was 
accompanied by clinical symptoms. After the first year, 
maternal antibodies no longer play a protective role, 
which suggests that other protective mechanisms come 
effectively into play from the first reinfection onwards, 
and that these are independent of the cumulative expo- 
sure to a great variety of malarial antigens. 
Acknowledgements 
This work was supported by grant no. 87W0043-Eureka from 
le Ministère de la Recherche et de l'Enseignement Supérieur 
(Paris). We thank Prof, L. H. Pereira da Silva for his constant 
support and encouragement. 
I ,  
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Received 2 July 1992; revised 28 September 1992; accepted 
for publication I October I992 


Malaria attacks in children exposed to high transmission : who is protected ?

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