Redalyc.Epidemiological Study of Paracoccidioidomycosis and Histoplasmosis in a Suburb of San Félix City, Bolívar State, Venez

Investigación Clínica ISSN: 0535-5133 [email protected] Universidad del Zulia Venezuela

Cermeño, Julman; Cermeño, Julmery; Godoy, Gerardo; Hernández, Isabel; Orellán, Yida; Blanco, Ytalia; Penna, Salvador; García, Luily; Mender, Thamara; Gonsálvez, Marisa; López, César; Hernández, Neudys; Longa, Isabel; Gottberg, Esther; Basanta, Amarilys; Castro, Milagros; Millán, Iraida; León, Walesca; Plaz, Flor; Jahouhari, Caroline; Cabello, Ismery Epidemiological study of paracoccidioidomycosis and histoplasmosis in a suburb of San Félix city, Bolívar state, Venezuela. Investigación Clínica, vol. 50, núm. 2, 2009, pp. 213-220 Universidad del Zulia Maracaibo, Venezuela

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Epidemiological study of paracoccidioidomycosis and histoplasmosis in a suburb of San Félix city, Bolívar state, Venezuela.

Julman Cermeño1, Julmery Cermeño1, Gerardo Godoy1, Isabel Hernández1, Yida Orellán1, Ytalia Blanco1, Salvador Penna1, Luily García2, Thamara Mender1, Marisa Gonsálvez1, César López2, Neudys Hernández2, Isabel Longa2, Esther Gottberg2, Amarilys Basanta2, Milagros Castro2, Iraida Millán2, Walesca León2, Flor Plaz2, Caroline Jahouhari1 and Ismery Cabello1. 1Escuela de Ciencias de la Salud “Dr. Francisco Battistini Casalta”, Universidad de Oriente Núcleo Bolívar, Ciudad Bolívar y 2Hospital “Raúl Leoni”. San Félix, estado Bolívar, Venezuela. Key words: Epidemiology, histoplasmosis, paracoccidioidomycosis, Venezuela.

Abstract. Epidemiologic studies of deep mycosis have been scarce in Bolívar state, where paracoccidioidomycosis and histoplasmosis are considered as endemic diseases. The aim of this study was to determine paracoccidioidomycosis and histoplasmosis prevalences in people from a suburb of San Félix, Bolívar state, Venezuela. Three-hundred volunteers agreed to participate in this study and they were inoculated with paracoccidioidine and histoplasmine. Identification and epidemiologic data were registered. Reading of skin tests after 24 hours was performed in 275 persons. Paracoccidioidine test was positive in 10.2% (n=28). A higher percentage of positive reactions in the age group of 40-50 years old (n=10; 35.7%) was observed. Bricklayers, farmers and miners were positive in 27.3 % (3 out of 11), a higher percentage than in people with other occupations. Histoplasmine test was positive in 7.6% of cases (n= 21). The higher percentage of reactivity was observed in the age group of 40-50 years old (n=9; 42.9%). There was a direct proportional relationship between staying time in the locality and H. capsulatum infection mainly in persons staying in the area for more than 30 years (p<0.05). These results showed low prevalences of P. brasiliensis and H. capsulatum infection in this area.

Corresponding author: Julman R Cermeño. Avenida 17 de Diciembre, Centro Comercial Country, piso 1, local 3. Ciudad Bolívar 8001, Venezuela. Tele/Fax: +58-85-6316923 +58-85-65-43291. E-mail: [email protected] 214 Cermeño y col.

Estudio epidemiológico de la paracoccidioidomicosis e histoplasmosis en una población suburbana de San Félix, estado Bolívar, Venezuela. Invest Clin 2009; 50(2): 213 - 220

Palabras clave: Epidemiología, histoplasmosis, paracoccidioidomicosis, Vene- zuela.

Resumen. El estudio epidemiológico de las micosis profundas ha sido es- caso en el estado Bolívar donde la paracoccidioidomicosis e histoplasmosis son endémicas. El objetivo de este estudio fue determinar la prevalencia de infecciones por Paracoccidioides brasiliensis e Histoplasma capsulatum en individuos residenciados en una población suburbana de San Félix, estado Bolívar, Venezuela. Se administró paracoccidioidina e histoplasmina a 300 personas voluntarias. Se realizó lectura de las pruebas a las 24 horas. La paracoccidioidina fue positiva en el 10,2% (n=28). Se observó mayor porcentaje de positividad en el grupo de 40-50 años (n=10; 35,7%). Las ocupaciones de riesgo: al- bañiles, agricultores y mineros, presentaron un porcentaje de positividad de 27,3% (3 de 11), mayor que el de los individuos sin riesgo aparente: mecáni- cos, oficios del hogar y estudiantes (25 de 264; 9,5%) (p=0,04). La histoplasmina fue positiva en el 7,6% (n=21). El mayor porcentaje de intradermorreac- ción positiva se observó entre los 40-50 años (n=9; 42,9%). Hubo relación sig- nificativa entre el tiempo de residencia en la localidad y la infección por H. capsulatum, demostrándose en los individuos con más de 30 años en esa localidad (p<0,05). Estos resultados muestran una prevalencia relativamente baja de infecciones por P. brasiliensis ydeH. capsulatum en el área estudiada.

Received: 29-04-2008. Accepted: 16-10-2008.

INTRODUCTION high organic content for H. capsulatum) that determine the distribution of these Paracoccidioidomycosis (PCM) and fungi in nature (1, 6-10). histoplasmosis (H) are systemic mycosis PCM is a chronic progressive infection produced by geophilic dimorphic fungi with a geographic distribution limited to Paracoccidioides brasiliensis and Histoplas- the Americas, specifically the Latin Ameri- ma capsulatum, respectively (1-3). These can countries. It is characterized by a pri- mycosis are endemic diseases in the south mary lung infection, frequently unapparent, of Venezuela and are considered as a public which can disseminate, principally present- health problem (4, 5). They are probably re- ing lesions on the mucosae of the upper air- lated to environmental conditions like hu- ways and upper digestive tract and occa- midity, temperature and soil characteristics sionally the gastrointestinal tract. The (10-28°C, pluviometry 500-2500 mm/year, lymph nodes are frequently involved and oc- acid soils with rivers around for P. bra- casionally the disease extends to other or- siliensis and 22-29°C, pluviometry 1200 gans, especially the skin tissue and adrenal mm/year, humidity 67-87 % and soils with glands (11).

Investigación Clínica 50(2): 2009 Paracoccidioidomycosis and histoplasmosis in suburb region of Venezuela 215

Histoplasmosis is almost always ac- PATIENTS AND METHODS quired by inhalation of the mycelial frag- ments and microconidia of the organism Geographic characteristics from an environmental source, most com- This study was performed in the com- monly disturbed earth or bird or bat drop- munity “25 de Marzo”, a suburban area pings. The organism is found worldwide and with 46309 inhabitants (19). It is localized it is endemic in parts of the United States, in Caroni county, San Felix city, situated in South America, Southeast Asia, Africa, and the north-east region of Bolívar state in Australia. Usually H presents as a dissemi- south-east of Venezuela. It has a mean an- nated infection with fever and weight loss. nual precipitation of 1000 mm3 and a rela- Respiratory complaints, local or generalized tive humidity of 70% (20). lymphadenopathy, hepatosplenomegaly, co- lonic lesions, and skin and oral ulcers may Samples also be present. Diagnosis is usually made A group of 300 persons voluntarily by culturing the fungus from blood or other agreed to participate in this study. Preg- clinical specimens, or by histopathologic nant women, children under 6 months old, examination of bone marrow aspirate or bi- adults older than 65 years old and people opsy material (9, 12). with a history of systemic mycosis were ex- Intradermic tests like paracoccidioid- cluded. Identification and epidemiologic ine and histoplasmine are often used in data was registered. epidemiologic studies in order to detect PCM and H respectively (6, 13, 14), particu- Clinical and laboratory evaluation larly in cases of asymptomatic infections. In of symptomatic patients these tests, fungus antigens are intrader- All patients with respiratory symptoms mically injected to induce a reaction that is were clinically evaluated and a radiological read 24 and 48 hours later and a positive study of the thorax was made. Sputum sam- reaction is an indurated area of 5 mm or ples were collected in patients with a proba- more. A positive reaction suggests the pres- ble diagnosis of PCM and/or H. All secre- ence of fungus infection (13, 15-17). tions were evaluated with Ziehl Neelsen Epidemiologic studies of deep mycosis stain, KOH 20% and argentic methenamine have been scarce in Bolívar state, even stain. All samples were cultured, by dupli- though PCM and H are considered as en- cate, in glucose agar Sabouraud and demic diseases (5, 18) and, therefore, it is heart-brain agar; they were incubated at necessary a better knowledge of the clinical 37°C during 8 weeks. In addition, antibod- and epidemiologic aspects of these dis- ies against H. capsulatum and P. brasilien- eases. sis in serum samples were determined. Most of cases of PCM and H in children All samples were processed in the Par- that have been diagnosed in “Raúl Leoni” asitology and Microbiology Department, Hospital in San Félix, Bolivar state, came Universidad de Oriente, Núcleo Bolívar. from the “25 de Marzo” community, for that reason this place was chosen to realize Serological study this epidemiologic study in order to deter- Before cutaneous tests were per- mine prevalence of P. brasiliensis and H. formed, blood samples were taken for serol- capsulatum infections in people living in ogy. To demonstrate specific antibodies this zone. against P. brasiliensis and H. capsulatum, GP43 antigen of P. brasiliensis (gently sup-

Vol. 50(2): 213 - 220, 2009 216 Cermeño y col. plied by Dr. Zoilo Pires de Camargo, Sao was developed (16, 17). Positive reactions Paulo, Brasil) and H. capsulatum antigen were considered indicative of past, inter- from Meridiam Bioscience Inc. (Cincinnati, current of subclinical infection by P. Ohio, USA, 45244) were used. Immunodif- brasiliensis or H. capsulatum. fusion test in agarose gel was performed as advised by the manufacturer. Detection of Statistical analysis H and/or M band was considered positive Chi-square test and exact test of Fisher for H. capsulatum and presence of any iden- were performed with a significance level of tity band was considered positive for P. p<0.05 using SPSS program, version 7.5 brasiliensis. for Windows.

Cutaneous tests RESULTS P. brasiliensis and H. capsulatum var capsulatum antigens were used and they Serological study were made in the Institute of Biomedicine, Specific antibodies against H. Universidad Central de Venezuela, Caracas. capsulatum (H and M bands) were not dem- Paracoccidioidine is a polysaccharide onstrated in any patients. Only in a case di- obtained from the yeast phase of 8-9 iso- agnosed as PCM, specific antibodies against lates of P. brasiliensis. Histoplasmine is a P. brasiliensis were detected. metabolic antigen obtained from the fila- mentous phase of H. capsulatum (21). Cu- Paracoccidioidine intradermic test taneous tests were realized after extraction A group of 300 intradermic tests was of blood samples to determine specific anti- performed, but in 25 individuals (8.4%) the bodies against P. brasiliensis and H. results could not be evaluated. Two hundred capsulatum. During the test, 0.1 mL of seventy five persons with a mean age of 17.3 paracoccidioidine was intradermically in- ± 15.6 years old, in a range from 7 months jected in the anterior face of the proximal to 63 years old, were evaluated; the largest third of left forearm and 0.1 mL of histo- age group was under 10 years old (n=129; plasmine in the anterior face of the proxi- 46.9%). Feminine gender was represented by mal third of the right forearm of each per- the 61.5%. The 86.9% (n=239) of evaluated son, simultaneously. Inoculation area was persons came from “El Progreso” (n=129; identified with a mark. Disposable syringes 46.9%), and “El Porvenir” zones (n=110; of 1 mL and 27 gauge needles were used. 40%), with a mean of 7.6 ± 8.4 years living Readings were made only at 24 hours inthoseplaces(range1monthto46years). after the injections because the subjects ac- 52% (n=143) was unemployed and 20% cepted to participate in the study during (n=57) was homeworker. only two days: the first day, when clinical The intradermic test was positive at 24 data would be collected and cutaneous hours in 10.2% (n= 28) of them. Reactivi- tests would be applicated; and the following ties to paracoccidioidine by age groups are day, when the readings would be realized; in Table I. The age group of 40-50 years old as at 24 hours many subjects have already was the group with the highest percentage reacted to these cutaneous tests (22), we between paracoccidioidine reactors (n= 10; considered the results would be valid. The 35.7%) and feminine gender (71.4%; n= 20) tests were considered positive when an en- had the highest percentage of positivity. dured and edematous area with a diameter High risk workers like bricklayers, of 5 mm or more in the place of inoculation farmers and miners showed a percentage of

Investigación Clínica 50(2): 2009 Paracoccidioidomycosis and histoplasmosis in suburb region of Venezuela 217 positivity (27.3%; 3 out of 11) significantly 39 patients were evaluated and only one higher than that in persons without an ap- case was diagnosed with PCM by demon- parent risk like mechanics, houseworkers stration of the fungus in sputum stains and and students (9.5%; 25 out of 264) (X2 culture. In addition, specific antibodies in =3.94;1 df, p=0.04). See Table II. Time liv- serum were detected. Clinical features were ing in the area was not associated with chronic cough, loss of weight and mucous positivity in the test. expectoration. Bilateral diffuse infiltrates In the group with positive intradermo- were observed in the thorax radiography. reaction, 6 (21.4%) were smokers, 14 (50%) This patient was treated with Itraconazole non smokers and 8 (28.5%) ex-smokers. 200 mg/day and periodic control. Collateral effects of the test were only observed in 8.4% (n=23), the most fre- Histoplasmine intradermic test quent were erythema (n=6; 26.1%) and In a similar way, this test was given to pruritus (n=6; 26.1%); less common were 300 persons and the reading at 24 hours af- general malaise, edema, low fever, sore terwards could only be realized in 275 indi- throat and local burning. With regard to viduals. The intradermic histoplasmine reac- chronic respiratory symptomatic patients, tion was positive in 7.6% of cases (n= 21).

TABLE I REACTIVITY TO PARACOCCIDIOIDINE AND HISTOPLASMINE BY AGE GROUPS IN THE “25 DE MARZO” POPULATION, SAN FÉLIX, BOLIVAR STATE. VENEZUELA

Age groups (years) Paracoccidioidine Histoplasmine 0-10 7* (5.4)/129 2 (1.6)/129 11-20 1 (2.0)/50 2 (4.0)/50 21-30 3 (10.3)/29 0/29 31-40 5 (16.1)/31 4 (12.9)/31 41-50 10 (35.7)/28 9 (33.3)/27 51-60 0/5 2 (40.0)/5 > 60 2 (50.0)/4 2 (50.0)/4 Total 28 (10.2)/275 21 (7.6)/275 *Number of reactor/Numbers of tested subjects. Values in parenthesis are percentages.

TABLE II RELATIONSHIP BETWEEN REACTIVITY TO PARACOCCIDIOIDINE AND HISTOPLASMINE AND OCCUPATIONAL OR RECREATIONAL EXPOSITION IN THE “25 DE MARZO” POPULATION, CIUDAD BOLÍVAR. BOLÍVAR STATE, VENEZUELA

Occupational Paracoccidioidine* Histoplasmine** or recreational Positive Negative Total Positive Negative Total exposition n (%) n (%) n (%) n (%) n (%) n (%) Yes 3 (10.7) 8 (3.2) 11 (4.0) 4 (19.0) 7 (2.7) 11 (4.0) No 25 (89.3) 239 (96.7) 264 (96.0) 17 (80.9) 247 (97.2) 264 (96.0) Total 28 (10.2) 247 (89.8) 275 (100) 21 (7.6) 254 (92.4) 275 (100) *X2= 3.94. 1 df. p=0.04. **X2= 13.407. 1 df. p= 0.006. n=number of individuals.

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Reactivities to histoplasmine by age ine and 25.7% and 19.6% at 24 hours for groups are in Table I. The age group of histoplasmine (4,18). This difference could 40-50 years old was the group with the be explained by the presence of rivers and highest percentage between histoplasmine lagoons around this area, a favorable envi- reactors (n= 9; 42.9%), followed by the age ronment for the development of P. group 30-40 years old (n=4; 19.0%). The brasiliensis (10). 61.9% (n=13) of histoplasmine reactors However, frequency of positivity to were feminine. paracoccidioidine was lower than in other A direct proportional relationship be- endemic regions of Venezuela, i.e. Sierra de tween the time living in this place and the Perijá (Zulia state), Paracotos (Miranda presence of H. capsulatum infection was state), Culebra island (Carabobo state) and statistically significant, particularly in per- Sierra de San Luis (Falcón state), with a sons living there for more than 30 years positivity of around 60% (15, 16, 24, 25) (X2=27.86; 2 df, p<0.0001). and than other endemic Latino American There was no evidence of a significant regions: Chaco province of Argentina (26) relationship between contact with birds or and Serra de Pereiro, Ceará, state of Brasil, fowls or visiting caves and positivity to where 32.1% of positivity was found (13). histoplasmine test. However, a significant Although, in this study, the reactivity to association between occupational risk both antigens might have been higher if the (farmers) and H. capsulatum infection was reading had been done at 48 hours, as has shown (see Table II) (Exact test of Fisher, been found in other study (18). p= 0.006). In endemic areas of Central América, a high prevalence of histoplasmine reaction DISCUSSION ranging from 12% to 40.4% has been observed in persons who have visited caves re- Intradermic tests like paracoccidioid- cently (3, 27, 28): 12% in Martinica (23) ine and histoplasmine have been very useful and between 13.2%-28.8% in Cuba (6, 29), in epidemiologic studies to investigate prev- higher than the prevalence found in this alence of subclinical infection of P. study. This difference might be in relation brasiliensis and H. capsulatum in endemic with ausence of caves in this area and the areas (14, 17, 23). Furthermore, these tests early reaction reading, before a posible are simple to use and easily evaluate the peak of reactivity at 48 hours (18). immune response, but are not diagnostic by Children infection in endemic areas is themselves. In this study we found 12 cases high (10). Young adults and children are (4.4%) positive to both tests. Thus, it may considered as epidemiologic markers since correspond to a cross-reaction with either they may have less chance to be in contact other primary pathogens, saprophytes or with fungus (16,30). Thus, the finding of between each other, a common feature in people under 20 years old with positive intradermic tests (10, 13, 16, 21). intradermic reaction could be an indicator In this study, a higher proportion of of the presence of fungus in the soil in the persons reacting to paracoccidioidine studied area. (10.2%) than to histoplasmine (7.6%) was It is pointed out that precocious infec- found, differing from studies carried out in tion in children under 10 years old by P. other zones of Bolivar state, where brasiliensis (1.6%) and H. capsulatum positivity was higher to histoplasmine: 8.5% (5.4%) is not negligible, although it is and 11.3% at 24 hours for paracoccidioid- much lower than that found in zones of Ar-

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