R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 7 ( l ) : 3 9 - 4 2 , j a n - m a r , 1 9 9 4
R E L A T O D E C A SO
LEPTOSPIROSIS PATIENT W ITH AIDS TH E FIRST CASE
REPORTED
E liza b e th d e S ou za N ev es, M arth a M a ria P ereirá, M a ria C lara G u tierrez G a lh a rd o , A d ria n a C aro li, Jarbas A n d rad e, M ariza G on ça lv es M o rg a d o a n d
R in a ld o P oncio M endes
A c a se o f re n a l icterohaem orrhagic lepto spirosis involving a p a tie n t w ith a cq u ire d im m unodeficiency syn d ro m e (AIDS) is reported. D espite th e low levels o f CD 4 + T lym p h o cy te s, the clinical co u rse o f lepto spirosis w as sim ilar to th a t o b se rve d in n o n -im m u n o d e p ressed p a tie n ts, a n d no w o rsening o f A ID S o ccurred due to the infebtion by th e spirochete. S ero lo g ic co n v ersio n w as o b se rve d in the m icroscopic agglu tination test, with m a xim u m titer o f 1:3,2 00. The p a tie n t h a d p o sitiv e urin e cu ltu res f o r Leptospira interrogansf o r tw o m onths, w h erea s b lo o d cu ltu re s w ere negative.
K ey-w o rd s: L eptospirosis. Case report. Leptospira interrogans. AID S.
T he acquired im m unodeficiency syndrom e (AIDS) is apandem ic disease o f growing importance, w ith 29,644 cases reported in Brazil by August 1992s. The city o f Rio de Janeiro is the second in the country in num ber o f patients, with 3,593 cases notified by the same date and w ith an incidence of 64.8 p er 100,000 inhabitants7. In turn, leptospirosis is endemic, w ith epidemic outbreaks occurring during the sum m er months due to the m ore intensive rainfall. A total o f 863 cases have been notified from 1987 to 1991, 55.5% o f which caused by an epidem ic in the summer o f 1988s.
W e r e p o r t a c a se o f le p to s p ir o s is (icterohem orrhagic form) involving a patient with G roup IV C 2AIDS.
CASE REPO RT
A mulatto male has been followed up at the V irology O utpatient Clinic o f the Evandro Chagas H ospital (ECH) since 1987 because o f AIDS and lymphatic tuberculosis. HIV infection was confirmed by the presence o f specific serum antibodies detected by ELISA and by indirect immunofluorescence, and tuberculosis was determ ined by the detection o f
Hospital Evandro Chagas/Departments of Bacteriology and Immunology, Instituto Oswaldo Cruz/Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
Address to: Dra. Elizabeth de Souza Neves. Hospital Evandro Chagas/FIOCRUZ. Av. Brasil 4365,21045-900Rio de Janeiro, RJ; Fax 55 21 590-9988 Brazil.
Recebido para publicação em 08/10/93.
alcohol-acid-resistant bacilli in the histopathological examination o f a lymphnode biopsy.
Specific tripletreatment of tuberculosis consisted o f rifampicin and isoniazid for six m onths in combination with pyrazinam ide during the first tv/o months. Isoniazid was also used for suppressive treatment.. Typing o f lym phocyte subpopulations by flow cytometry at the time o f treatment indicated 255 CD4 -^ T lym phocytes and 1018 C D 8 + lym phocytes/mm3. The CD4 + /C D g + ratio was 0.25.
The patient gave up treatm ent in Decem ber 1988, and returned to our Service in A ugust 1991, w ith oral candidiasis and a 14kg w eight loss, with no fever or other manifestations o f reactivation o f tuberculosis. He had not been taking any medication since the time when he stopped treatment. Nystatin was introduced for the treatment o f candidiasis, together w ith sulfam ethoxazole-trim etoprim for primary prophylaxis ofpulm onary pneum ocystosis, 500mg/day zidovudine, and 7,200,000 IU penicilin G benzatine as total dose for the treatm ent o f late secondary syphilis, because o f the detection o f positive VDRL test w ith 1/64 titer and normal cerebrospinal fluid. T hepatient has been com plying w ith the above treatment and has been follow ed up at the Service since he reappeared in A ugust 1991.
In August 1992, he came to the EC H 13 days after falling in a ditch in the slum w here he lived presenting high fever, m yalgia predom inating in the lower limbs, vom iting and headache lasting 6
R e la to d e C aso. N e v e s E S, P e re ira M M , G a lh a rd o M C G , C aroli A , A n d ra d e J , M o rg a d o M G , M e n d e s RP. L e p to s p ir o s is p a tie n t w ith A ID S th e f i r s t c a se reported. R ev ista d a S o c ie d a d e B ra sile ira d e M e d ic in a T ro p ica l 2 7 :3 9 -4 2 , ja n - m a r , 1994.
days. H e had been presenting jaundice, epistaxis and reduced urinary output for 2 days. Arterial pressure, 80x60m m Hg; heart rate, 80 beats per minute; respiratory rate, 20 inspirations perm inute; a x illa r y te m p e r a tu re , 3 6 .5 °C . N e u ro lo g ic , pulm onary and cardiac examination w ere norm al. The abdom en was painful upon superficial and deep palpation, w ith spleen palpable 1cm from the left coastal m argin. N o skin lesions. Em ergency biochemical blood tests revealed 184mg/dl urea, 5 .3 m g /d l creatin in e, 140m E q/l sodium , and 4.3m E q/l potassium . Blood counts revealed 33% hem atocrit, 3,000,000 red cells/mm3, 10.7g/% hem oglobin, 2,500 leukocytes/m m 3 (0/1/0/0/2/82/ 14/1), and 32,000 platelets/m m 3. Prothrom bin activity was 60% , and a chest X-ray was normal.
W ith a diagnostic hypothesis o f leptospirosis, later confirmed by the microscopic agglutination* test and by the isolation o f L e p t o s p i r a i n t e r r o g a n s
in urine cultured in Ellinghausen medium (EM JH)4 (Table 1), w ater and electrolyte repletion was started and dopam ine, diuretics and a platelet concentrate w ere introduced. A hematological evaluation was m ade 28 days after the onset o f sym ptoms. T he patient presented a low num ber of lymphocytes (550/m m 3) from which a small fraction reacted w ith monoclonal antibodies specific for CD4+ T lym phocytes (13/mm3) and CDg + T lym phocytes (68/m m 3). The CD4 + /C D g+ ratio was also reduced (0.19) in relation to the first examination.
The patient’s course was satisfactory, with regression o f renal insufficiency on the 7th day of
hospitalization. However, he continued to have daily fever, w ith no relation to a specific tim e o f day and not exceeding 38.5°C. N o chills w ere present.
To clarify the origin o f fever, blood, urine, sputum and bone m arrow cultures w ere perform ed, and lymphnode, liver and bone m arrow biopsies were taken. Since the cultures w ere negative and the biopsies inconclusive, em pirical treatm ent o f tu b e rc u lo sis w ith rifa m p ic in , iso n ia z id and pyrazinamide was introduced and discontinued after one month due to the absence o f a response and to the presence of signs o f liver toxicity. The patient was discharged on October 16, 1992 in improved general condition and with decreased fever intensity.
On the occasion o f the first réévaluation at the outpatient clinic 12 days after discharge from the hospital, the results o f the L e p t o s p i r a s p . cultures were available. Blood cultures in EM JH medium w ere negative, but urine culture revealed the growth o f L e p t o s p i r a i n t e r r o g a n s up to the 60th day of- d isease. T he e v o lu tio n o f the m ic ro sc o p ic agglutination titers and the results o f the cultures are presented in Table 1. In view o f these results, tetracycline was adm inistered at a daily dose o f 2g for 21 days, since serology continued to be positive also for syphilis.
When the patient was evaluated again 13 days later he was asymptomatic and had gained 7kg. Another urine culture for L e p t o s p i r a s p . gave negative results.
In January, 1993, signs o f dementia associated with progressive cachexia appeared. The patient was admitted to the hospital twice, w ith severe
Table 1 - R esu lts o f serum m icroscopic agglu tination te st (1:), a n d blo o d a n d urine culture to L ep to sp ira sp in A ID S patient.
Day o f ilness Serovar Culture
1 2 3 4 blood urine
6“' 0 0 0 0 ND ND
10th 3,200 0 0 0 - +
60th 1,600 800 400 400 - +
70ih 1,600 800 400 100 _
-100“1 400 200 0 0 -
-ND - not done; Serovar: 1 = icterohaem orrhagiae', 2 = copenhagenr, 3 = s e n to t; 4 = p a lo c
* Note: the serovars used in the m icroagglutination test w ere: ic te ro h a em o irh a g ia e , c o p en h a g e n i,ja v a n ic a , c a n ico la , castellonis,
p y r o g e n is , c yn o p teri, auturnnalis, sen to t, d ja sim a n , australis, p o m o n a , g rip p o typ h o sa , h e b d o m a d is, w oljfi, se jro e , sa x k o eb in g , b a ta via e, ta ra sso vi, p a n a m a , a n d a m a n a , celled o n i, sherm ani.
R e la to d e C aso. N e v e s E S, P e re ira M M , G a lh a rd o M C G , C aroli A , A n d ra d e J , M o rg a d o M G , M e n d e s R P. L e p to sp iro sis p a tie n t w ith A ID S th e f i r s t c a se rep o rted . R e v ista d a S o cied a d e B ra sile ira de M e d ic in a T ro p ic a l 2 7 :3 9 -4 2 , ja n - m a r , 1994.
w eight loss, fever, confusion, and developed septicemia and acute renal insufficiency, dying one m onth later. Blood and urine cultures taken one day before death w ere negative to L e p t o s p i r a s p .
M icroscopic agglutination test gave a titer o f 1:100 to serovar L e p t o s p i r a i c t e r o h a e m o r r h a g i a e .
A t the au to p sy , the cause o f death w as bronchopneum onia due to Gram-negative cocci. H IV -related subacute encephalitis and muscular a tro p h y w e re o b s e rv e d . F in a lly , cach ex ia, m olluscum contagiosum , dermatophytosis, gastric erosions, acute pancreatitis w ith steatonecrosis, m ultiple septic pulm onary infarct and herpesvirus colitis w ere also present. Leptospirosis lesions w ere not observed and silver stain did not reveal spirochaetal forms.
DISCUSSION
H um an immunodeficiency virus (HIV) leads to dysfunction o f the im munologic system, with the consequent occurrence o f infections w hich depend on a faulty cell immune response. Thus, infections caused by opportunistic agents such as P n e u m o c y s ti s c a r i n i i , C y t o m e g a l o v i r u s and C r y p t o s p o r i d i u m s p .
start to be observed3.
The occurrence o f leptospirosis, in turn, depends on exposure o f susceptible individuals to w ater or soil contam inated w ith infected urine containing
L e p t o s p i r a i n t e r r o g a n s . Laborers, animal breeders, m iners, urban sanitation w orkers, butchers, and veterinarians represent the occupational group at risk to contract leptospirosis in areas where the disease is endemic4. In Brazil, however, individuals living in dwellings with inadequate basic sanitation, such as city slums, are more exposed to the infection6. T he case described here was the first report of a s s o c ia tio n o f le p to s p iro s is w ith a c q u ire d im m u n o d e ficien c y sy n d ro m e. T w o cases o f leptospirosis in HIV-infected patients have been reported9. The authors reported that the coexistence o f the two entities did not interfere with the evolution o f either. Sim 'a rly , in the present study no change in the behavior o f AIDS or o f leptospirosis was observed.
Yamashiro-Kanashiro et al10 demonstrated that patients w ith leptospirosis present an im portant reduction o f the cell immune response as determined by functional tests and by evaluation o f mononuclear
cell subpopulations, w ith depletion o f CD4 + T lymphocytes and total (CD3 + ) T lym phocytes. The present patient had very low total lym phocyte levels as well as very low levels o f the CD4 + and CD8 + T su b p o p u latio n s w h ic h , h o w e v e r, d id n o t s ig n ific a n tly in te r f e r e w ith th e c o u r s e o f leptospirosis. This suggests that the mechanism of leptospire elim ination is not exclusively related to helperT cells. However, the maximum agglutinating antibody levels w ere lower than those detected in most o f the cases observed in Brazil2. This finding may perhaps be explained by the im munodepression o f the patient caused by AIDS.
We should point out the persistence o f a positive urine culture for L e p t o s p i r a i n t e r r o g a n s over a long period o f time, a fact observed only in a small percentage o f patients1.
Finally, the absence o f any evidence o f persistent leptospirosis at autopsy must be emphasized.
RESUM O
Os au to res relatam um ca so d e fo r m a íctero-hem orrágica d e leptospirose oco rrid a em p a c ie n te com síndrom e d e im u n o d eficiên cia a d q u irid a (SID A). A ev o lu çã o clín ic a d a le p to sp iro s e s e d e u d e m o d o s e m e l h a n t e a o o b s e r v a d o e m p a c i e n t e s s e m im unodepressão, a p e sa r d o s n íveis m uito b a ix o s d e linfócitos T CD4 . T am pouco h o u ve a g ra v a m e n to da SIDA em d ec o rrê n cia d a infecção p e lo espiroqueta. O b s e r v o u -s e c o n v e r s ã o s o r o ló g ic a n a p r o v a de aglutinaçãom icroscópica com títulos m áxim os d e 1:3.200. O p a c ie n te p e r m a n e c e u p o r d o is m e se s com u rinocultura p o s it iv a p a r a L e p to s p ira in te rro g a n s , s e n d o a s
hem oculturas negativas.
P ala vras-chaves: L ep to sp iro se. R ela to d e caso. Leptospira interrogans. SIDA.
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