R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 1 ( 2 ) : 5 1 -5 4 , A b r - J u n , 1 9 8 8 .
IN F R E Q U E N C Y O F A S Y M P T O M A T IC M A L A R IA I N A N E N D E M IC A R E A IN A M A Z O N A S , B R A Z IL
Aluizio Prata, Margarita Urdaneta, Patrick B. McGreevy
and Mauro Shugiro Tada
A m a la ria su rvey w a s c o n d u c te d in a n area o f h ig h tra n sm issio n ( C o sta M a rq u e s, R o n d o n ia , B r a z il) to d eterm in e th e p re v a le n c e o f a s y m p to m a tic p a r a s ite m ia a n d its c lin ic a l sig nificance. M o s t o f th e p e o p le su rv e y e d were im m ig ra n ts who h a d liv e d in th e en d em ic a rea < 5 yea rs. T h e p e o p le h a d ea sy access to fr e e d ia g n o stic a n d tre a tm e n t services a t th e M a la r ia C lin ic in th e to w n o f C o sta M a rq u e s. T h e p re v a le n c e o f p l a s m o d i a l p a r a s ite m ia in 3 4 4 p e o p le w as 2 2 % . T h ere were 3 6 in d iv id u a ls with
a sy m p to m a tic in fectio n s a m o n g the 77 p a r a s ite m ic p a tie n ts. D u r in g th e tw o d a y s fo llo w in g the in itia l e xa m in a tio n , 1 9 o fth e 3 6 in d ivid u a ls: w ith a sy m p to m a tic in fectio n s d evelo p ed m a la ria . A m o n g th e 17 p a tie n ts who r e m a in e d a s y m p to m a tic f o r > 2 d a ys, 4 h a d o n ly g a m eto cytes, 1 h a d ta k e n in a d e q u a te a n ti-m a la r ia l trea tm en t, 3 were u n d e r tre a tm e n t a n d 2 m oved. S i x a s y m p to m a tic p a tie n ts d e n ie d th e u se o f a n ti-m a la r ia l d ru g s a n d th e y d evelo p ed m a la ria 3 - 6 d a y s a fte r th e in itia l p a ra sito lo g ic a l d iagnosis. T he f i n a l p a tie n t rem a in ed a sy m p to m a tic d u rin g th e 7 d a y o b serva tio n p erio d . H e h a d a h isto ry o f > 4 0 m a la ria a tta c k s a n d d e n ie d th e use o f a n tim a la r ia l trea tm en t. W ith th e excep tio n o f the la tte r a ll o f the o th e r a sy m p to m a tic p a tien ts, were eith er in th e in cu b a tio n p e r io d o r h a d been tre a te d I t is co n clu d ed th a t a s y m p to m a tic m a la ria is rare in the C osta M a r q u e s area a n d th a t it is n ecessary to trea t a ll in d iv id u a ls w ith p la s m o d ia l p a ra site m ia .
K ey words: M alaria. A sym ptom atic m alaria. P la s m o d iu m fa lc ip a ru m . P la sm o d iu m vivax. Brazil.
Surveys in m alaria endem ic areas reveal plas m odial parasitem ia in variable percentages o f the people. M a n y tim es these p atients are asym ptom atic and their parasitem ia m ay indicate a state o f equili brium betw een the parasite and the h o st1458. T hese patients often refuse anti-m alarial treatm ent because they don’t feel sick, especially when th e prescribed drugs m ust be taken over m any days and produce side reactions. T his occurred on several occasions during ou r longitudinal stydy o f endem ic m alaria in the area o f C o sta M arques, R ondonia, B razil (12.° 2 6 ’S, 6 4p 14’W).
The objective o f the present study w as to determ ine the prevalence o f m alaria infection in the C o sta M arques area, and to define the clinical signi ficance o f p arasitem ia in individuals w ith asym ptom a tic infections.
M A TERIA L S A ND M ET H OD S
In C o sta M arques, m alaria is cau sed by P la s
m o d iu m fa lc ip a r u m and P la sm o d iu m vivax. D uring a
N ú c le o de M e d ic in a T ro p ic a l e N u tr iç ã o U n iv e rsid a d e d e B ra sília
7 0 .9 1 0 B ra sília , D F , B ra zil
T h is stu d y w a s su p p o rte d u n d e r a c o lla b o ra tiv e a g ree m e n t b e tw e e n th e U n iv e rs ity o f B ra s ilia a n d th e W a lte r R e ed A rm y
I n s titu te o f R e s e a rc h , g ra n t n u m b e r DA MD 1 7 -8 4 -G -4 0 0 7 .
R e c e b id o p a r a p u b lic a ç ã o e m 4 / 6 /8 8
25 d ay period in D ecem ber, 1986, w e conducted a
house to house survey o f residents along road BR 429
(from C o sta M arq u es to Présidente M édici) betw een kilom eters 3 and 62. E a c h person subm itted finger prick blood to prepare thick and th in films for routine
parasite exam ination. T he films w ere transported to
the M a laria C linic in the tow n o f C o sta M arques, stained with G iem sa and exam ined under oil im m er sion a t 1 00 0 X . O ne hundred fields w ere exam ined to detect the presence o f plasm odia. T o estim ate the density of plasm odia per m m3 o f blood the ‘parasite: leucocyte ratio ’ w as m ultiplied b y 5,000. This is the norm al num ber o f leucocytes p er m m3 o f blood in C o sta M arques (M . U rdaneta: personal com m uni cation, 1988). T h e ‘plasm odia: leucocyte ratio’ was determ ined from th e blood films by counting the num ber o f p arasites p e r 5 0 0 leucocytes or, alterna tively, the num ber o f leucocytes per 1 , 0 0 0 parasites, w hichever cam e first9.
W e returned to th e study population along B R 429 within 1-2 days after the initial exam ination to provide anti-m alarial drugs to th e parasitem ic patients and to inquire ab o u t sym ptom s, the num ber o f prior m alarial attacks, m edications in use and com pliance. P eople who developed sym ptom s before our follow-up visits had acess to free diagnosis and treatm ent a t the M a laria Clinic. Individuals w ith asym ptom atic infec tions were followed for 7 days.
P r a ta A , U r d a n e ta M , M c G r e e v y P B , T a d a M S . I n f r e q u e n c y o f a s y m p t o m a t i c m a l a r i a in a n e n d e m ic a r e a in A m a z o n a s , B r a z i l . R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 1 , 5 1 -5 4 , A b r -J u n , 1 9 8 8 .
RE S U LT S
D uring the survey we collected 344 sam ples o f blood. M icroscopic exam ination revealed th a t 77
(2 2 % ) were positive: 14 with .P. v iv a x and 63 w ith P.
fa lc ip a r u m . C linical exam ination revealed th a t 41 patients h ad sym ptom s w hen the p arasite diagnosis was established.
W e returned to the study area along the road 1 to 2 days after the initial visit to co n tact the 36 asym p
to m atic patients. T w o of them had m oved, 19 had
developed sym ptom s, an d 15 rem ained asym ptom atic. O f th e latter, 3 w ere infected w ithP. v iv a x and 12 with P. fa lc ip a r u m . T he patients w ith /1, v iv a x had 5 0 ,2 3 3
and 420 trophozoites per m m 3. A m ong the 12 with P.
fa lc ip a r u m there were 4 with only gam etocytes and 8 with only trophozoites. T h e highest trophozoite densi ty in the asym ptom atic group infected w ith P. fa lc i p a r u m was 41 ,1 6 0 parasites p e rm m3 (T ab le 1). T here
w as no relationship betw een the intensity o f parasi tem ia and the presence o f sym ptom s (T ab le 2).
W e treated the 19 sym ptom atic patients and the 4 asym ptom atic patients with falciparum gam etocytes. A m ong the 11 rem aining patients, 4 adm itted to taking anti-m alarial m edication (T able 3). Tw o children aged 8 and 11 y ears with parasite densities o f 491 and 316, respectively, were taking folk m edications and prefer red to continue this treatm ent. B lood exam ination two days later show ed th a t th eir parasite densities dropped to 4 0 and 0 trophozoites, respectively, and they were n o t visited again. O n e p atien t with an initial density o f 1,469 trophozoites w as taking m edication prescribed elsewhere. She h ad subsequent parasite densities of 7 5 0 a n d 50 trophozoites and was n o t follow ed further. T he final p atien t had an initial density o f 50 vivax trophozoites. H e h ad been treated incom pletely 15 days earlier and w as given new m edication.
T ab le
2
- R e la tio n s h ip betw een p a r a s ite d e n sity a n d th e p resen ce o f s y m p to m s a t f i r s t e x a m in a tio n in 53 p a tien ts.Parasites/m m 3
N.° P atien ts
P. fa lc ip a r u m P. viv a x
Sym ptom s N o sym ptom s Sym ptom s N o sym ptom s
< 9 9 4 7 0 1
100 - 999 8 9 0 3
1,000 - 4,999 3 5 0 0
5 ,0 0 0 - 14,999 4 3 1 0
1 5 ,0 0 0 - 19,999 1 1 0 0
2 0 ,0 0 0 - 4 1 ,9 9 9 0 1 0 0
42 ,0 0 0 - 80,000 2 0 0 0
T O T A L 2 2 26 1 4
5 2
T ab le 1 - A g e , sex, y e a r s in residence, d e n sity o f a s e x u a l p a r a s ite s o n in itia l e x a m in a tio n , a n d d a y o f in itia l s y m p to m s in m a la ria p a tie n ts.
A ge
(y ears) Sex
Y e a rs in residence
P a ra site s/m m 3
fa lc ip a r u m v iv a x
D a y of sym ptom s
33 M 4 0 92 1-2
57 M 7 0 668 1-2
8 F 7 9 0 1-2
34 M < 1 30 0 1-2
7 F 3 78 0 1-2
6 F 6 99 0 1-2
37 M < 1 2 8 9 0 1-2
22 F < 1 336 0 1-2
0.5 F < 1 3 67 0 1-2
25 F 7 837 0 1-2
9 M 3 1,198 0 1-2
4 0 F 3 1,650 0 1-2
39 M < 1 3,325 0 1-2
9 F 4 4 ,5 3 0 0 1-2
15 M 12 6 ,0 4 5 0 1-2
9 F 3 8 ,3 2 7 0 1-2
8 M < 1 8,385 0 1-2
5 M < 1 1 9,942 0 1-2
7 F 3 4 1 ,1 6 0 0 1-2
12 F 2 0 233 3
9 F 4 505 0 3
9 M 8 20 0 5
4 F 4 2 5 0 0 5
9 M 9 659 0 5
8 M < 1 0 42 0 6
6 F < 1 0 50 > 7
53 M 5 49 0 > 7
11 F 2 316 0 > 7
8 M 2 491 0 > 7
P r a ta A , U r d a n e ta M , M c G r e e v y P B , T a d a M S . I n f r e q u e n c y o f a s y m p t o m a t i c m a l a r i a in a n e n d e m ic a r e a in A m a z o n a s , B r a z il. R e v is t a da . S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 2 1 , 5 1 -5 4 , A b r -J u n , 1 9 8 8 .
T able 3 - A ge, d e n sity o f a se x u a l sta g es a n d fir s t d a y o f s y m p to m s in 11 p a tie n ts w ith p la s m o d ia l p a ra site m ia .
P a ra s ite s /m m 3 /D a y
A ge 0 1 2 3 4 5 6 7 R em arks
9 659
P. fa lc ip a r u m 1706
(S)
9 505 1950 (S )
9
4 20
250
20 (S ) (S )
8 491 40 F o lk
tre atm en t
11 316 0 F o lk
tre atm en t
6 1469 7 5 0 50 In
tre atm en t
53 4 9 10 0 C hloroquine
prophylaxis?
6 50
P. v iv a x
In com ple te treatm en t
12 233 193
(S )
8 420 57
(S )
(S ) *= d a y o f in itial sym pto m s.
The rem aining seven asym ptom atic patients were not taking m edication (T ab le 3). Six o f these patients becam e sym ptom atic betw een 3-6 days after the initial blood exam ination. In 2 o f th e 6 additional blood exam inations m ade before th e o n set of sym p tom s revealed sm all increases in the density o f asexual stage p arasites to a m axim um o f 1,950. In the third
patient, a subsequent count rem ained unchanged ( 2 0
P. fa lc ip a r u m ). T h e fourth p atien t did n o t have a follow-up blood exam ination. T he fifth and sixth patients h ad a d ecrease in the initial density o f vivax trophozoites 233 to 193 and 420 to 57.
T he rem aining p atient w as a 53 y ear old m an who had densities o f falciparum trophozoites o f 4 9 ,1 0 and 0 on days 0, 5, and 7, respectively, and he rem ained asym ptom atic throughout the study. H e claim ed to have h ad 40 episodes o f m alaria in the past, b u t h a d n o t experienced m alaria during the previous three years. H e attributed this fa c t to the use o f chloroquine for 1 1 /2 years in the past. H ow ever, six m onths later this m an reported to the M alaria Clinic with acute m alaria and we suspect th a t he was taking prophylactic m edicine during the present study. W ith the exception o f this m an, all o f the patients were treated for m alaria.
D IS C U S S IO N
T o determ ine the frequency of persistent para sitem ia w ithout sym ptom s o f m alaria in the residents o f C o sta M arq u es we followed 30 asym ptom atic people with asex u al stage plasm odia. N in eteen deve loped sym ptom s 1 - 2 days after the parasitic diagnosis was m ade. O f the 11 rem aining asym ptom atics, the parasitem ia was secondary in four o f them because th ey were under treatm ent. In 6 o f the asym ptom atics the initial diagnosis was m ade during the incubation period b ecause sym ptom s appeared w ithin th e n ex t six
days. There w as only one patient, the 53 y ear old m an,
w ith parasitem ia n o t associated with an acute episode o f malaria.
The low frequency o f asym ptom atic carriers in C o sta M arques contrasts sharply with d a ta from other countries13. F o r exam ple, in som e hyperendem ic areas o f A frica, asym ptom atic parasitem ia is frequen tly found in children and especially in adults4678. In these areas the prevalence o f m alaria, the density o f parasites, and the frequency o f sym ptom atic carriers are high in children and dim inish progressively with age. In the C o sta M arq ues area, we encountered w hat C hagas and C hagas noted over 50 years ago th a t “ ... there cannot be persistent parasitem ia w ithout sym p to m atic m anifestations”2.
A lthough there is high m alaria transm ission along road B R 429, there are factors th a t delay the acquisition o f im m unity to clinical disease in the local people. A m ong them are the short tim e o f residence in the endem ic a rea and access to free diagnosis and tre a tm e n t T hese factors reduce h ost-parasite co n tact and delay the acquisition o f im m unity to clinical disease.
In the C o sta M arq u es area, the presence o f asexual stage plasm odial parasitem ia in non-treated individuals im plies the necessity for tre a tm e n t I f th is is n o t prescribed, m alaria sym ptom s are likely to appear w ithin a week.
RE S U MO
j E m u m a á rea d e a lta tra n sm issã o d e m a lá ria (C o sta M a rq u e s, R o n d ô n ia ) f o i fe ito u m estu d o p a r a d e te rm in a r a p re v a lê n c ia d e p a r a s ite m ia a ssin to -m á tic a e seu sig n ific a d o clínico. A -m a io ria d o s h a b ita n tes e stu d a d o s era im ig ra n te q u e vivia na região há m e n o s d e 5 anos. E m C o sta M a r q u e s há fa c ilid a d e s p a r a o d ia g n ó stico e p r o n to tra ta m e n to d a m a lá ria . E m 3 4 4 p e s s o a s e x a m in a d a s h a via 77 (2 2 % ) co m p a r a s ite m ia p a r a h e m a to zo á rio s. E n tre estes, 3 6 n ã o tin h a m s in to m a to lo g ia d e m a lá ria . A p ó s d o is d ia s, 1 9 d o s 3 6 d esen vo lvera m s in to m a to logia. D o s 1 7 q u e c o n tin u a v a m a ssin to m á tico s, 4 tin h a m so m e n te g a m e tó c ito s no esfregaço d e sa n g u e
P r a ta A , U r d a n e ta M , M c G r e e v y P B , T a d a M S . I n f r e q u e n c y o f a s y m p t o m a t i c m a l a r i a in a n e n d e m ic a r e a in A m a z o n a s , B r a z i l . R e v is t a d a S o c ie d a d e B r a s ile ir a d e M e d ic in a T r o p ic a l 21 , 51 -5 4 , A b r -J u n , 1 9 8 8 .
e x a m in a d o , 1 tin h a recebido tra ta m e n to a n tim a lá -rico in a d eq u a d o , 3 esta v a m em tra ta m e n to e 2 se m u d a ra m d a área. E n tr e o 3.° e 6? d ia 6 a p re sen ta ra m sin to m a to lo g ia . U m p a c ie n te c o n tin u o u a ssin to m á -tico n o 7.° dia, q u a n d o te rm in o u a observação. E le c o n ta va j á ter tid o m a is de 4 0 a ta q u e s d e m a lá ria . E x c e to ele, to d o s o s o u tro s a ssin to m á tic o s ou esta va m no p e r í o d o d e in cu b a çã o ou e m tra ta m en to . C o n clu i-se q u e a m a lá ria a ssin to m á tic a é rara em C o sta M a r q u e s e q u e é n ecessário tra ta r to d o s os in d iv íd u o s co m p a ra site m ia .
Palavras-chaves: M alária. M a lá ria assintomática.
Plasm odium falciparum . Plasm odium vivax. B ra sil.
RE F ERE N C E S
1. B ru c e -C h w a tt L J . A lo n g itu d in al su rv e y o f n a tu ra l m a la ria in fec tio n in a g ro u p o f W e s t A fric a n ad u lts. P a r t
I a n d I I. W e s t A f r ic a n M e d ic a l J o u r n a l 1 2 :1 - 5 2 ,1 9 6 3 . 2 . C h a g as C , C h a g a s E . M a n u a l d e D o e n ç a s T ro p ic a is e
In fe c tu o s a s . V o lu m e I. L iv ra ria E d ito r a F r e ita s B a sto s.
R io d e J a n e ir o , 1 9 3 5 .
3. C o b ra n K M c L . M a la ria in th e p a rtia lly im m u n e a d u lt N igerian. T h e Jo u rn a l o f T ro p ic al M ed icin e a n d H y g ien e 6 0 :2 3 3 - 2 3 7 , 1 9 6 0 .
4 . G a m h a m P C C , W ils o n D B , S w ellen g reb el N H . A review o f h y p e re n d e m ic m a la ria . T r o p ic a l D is e a s e B ulletin. 4 7 :6 7 7 -6 9 8 , 1 9 5 0 .
5. G re e n w o o d B M . A s y m p to m a tic m a la ria in fectio n s -
D o th e y m atter? . P a ra s ito lo g y T o d a y 3 :2 0 6 - 2 1 4 ,1 9 8 7 . 6. M c G re g o r IA . T h e sig n ifican ce o f p a ra s itic in fectio n s in
term s o f c lin ic a l d ise ases: A p e rs o n a l v ie w . P arasito lo g y 9 4 (S u p p l.): 1 5 9 -1 7 8 , 1 9 8 7 .
7. O rg a n iz a c ió n M u n d ia l d e la S a lu d . Q u im io te ra p ia d e l P alu d ism o . S éries M o n o g ráficas. 2 7 . G in e b ra, 1982. 8. S c h w e tz J , P e e l M . C o n g e n ita l m a la ria a n d p la c e n ta l
in fectio n s a m o n g s t n e g ro es o f C e n tra l A fric a . T r a n s a c tio n s o f th e R o y a l S o c iety o f T r o p ic a l M e d ic in e a n d H y g ie n e. 2 8 :1 6 7 - 1 7 4 , 1 9 3 4 .
