Review on human mycoses in Venezuela

Darío Novoa-Montero, MD, PhD* y José A. Serrano, MD**

* Universidad de Los Andes, Facultad de Medicina, Unidad de Medicina Interna, Sección de Investigación, Laboratorio Multidisciplinario de Investigación Clínico-Epidemiológica (Lab-MICE).
** Universidad de Los Andes, Facultad de Medicina, Departamento de Patología, Unidad de Ultraestructura y de Estudio Multidisciplinario de Actinomicetales Patógenos del Hombre y del Suelo.

Note: This review is an update version of the conference "Human Mycoses in Venezuela". Abstract Book.
I International Symposium on Mycoses in the New Millenium- Challenges & Strategies. Society for Indian Human and Animal Mycologists. February 9th-11th, 2000.

Key-words: Human mycoses, histoplasmosis, coccidioidomycosis, AIDS.

Human Cutaneous and Superficial Mycoses in Venezuela

The following is a comprehensive review on the most relevant papers published on cutaneous and superficial mycoses in Venezuela (dermatophytoses, pitiriasis, candidiasis, onichomycosis, tinea nigra, otomycosis, ocular mycosis, and piedra).

Venezuela is a northern South American country set in the half north of the intertropical zone, in the so-called low latitudes. Its geographical position is between 0°45' and 12°11'46" (North latitude), and between 59°48' and 73°11'49" (West longitude). This country has tropical and subtropical climates. Most cases of human mycoses reported have been found in the States of Lara, Falcón, Zulia, Yaracuy and Carabobo. The State of Lara has been nicknamed the 'Eden of mycoses in Venezuela' (1). Altogether these five states may add up about 70% of the total cases of mycoses reported in Venezuela.

The current importance of the role of cutaneous and superficial mycoses in Venezuela (and in the world) stems on their emergent morbidity among selected groups who are engaged to antibiotic or corticosteroid therapies, women using oral contraceptives or patients using immunosuppressive drugs. In addition, the audiovisual (TV) adds suggesting a 'liberal' not medically prescribed use of antimycotic ointments, sprays, vaginal suppositories or tablets have notably contributed to increase the recurrence of human dermatophytoses and candidiasis infections, specially among patients with diabetes, hormonal disorders or obesity. Other risk factors for incidence and prevalence of human cutaneous mycoses infections in communities are the professional use of rubber and leader shoes, boots and thick clothes. According Albornoz (2), the public health impact of dermatomycoses has been the appearance of outbreaks in schools, platoons of soldiers, sport teams, and so forth.

Albornoz emphasizes the following facts: (a) the statistical data gathered by the Venezuela Ministry of Health are an overestimation of the 'true' prevalence of clinical mycoses (morbidity) since the final mycological laboratory diagnosis has usually been missing; (b) therefore, diagnoses as a whole have been clinically based, and only partially confirmed by mycological tests. In addition, not reported cases and groups of people with mycoses who do not ask for medical assistance, may produce an underestimation of the actual frequency of superficial mycoses in Venezuela (2).

Table 1, summarizes data on reported cases of cutaneous mycoses in Venezuela from 1984 to 1997. This table abridges a sequential series of tables published in the Boletín Informativo- Micosis en Venezuela, numbers 1 to 32(3). Between 1984 and 1997, Mycology Groups led by Albornoz pointed out that they had only confirmed about 57.7% (range 51.4% to 66.5%) mycological diagnoses out of the total reported clinical diagnoses. It might mean that about 6 out of 10 clinically suspected cases of cutaneous my coses among general Venezuelan population might suffer 'true' mycotic infections. Up to now the following eight cutaneous or superficial mycoses have been reported in Venezuela: dermatophytoses, candidiasis, pityriasis, otomy cosis, onichomycosis, ocular mycosis, tinea nigra, and piedra.

Years	Diagnosis		Percent of mycologically confirmed diagnosis
	Clinical	Mycologic
1984 - 1987	6.052	3.442	56,90%
1988 - 1989	2.731	1.404	51,40%
1989 - 1990	2.492	1.317	52,90%
1990 - 1991	-	-	-
1991 - 1992	1.948	1.080	55,40%
1992 - 1993	1.593	873	54,80%
1993 - 1994	-	-	-
1994 - 1995	2.528	1.682	66,50%
1995 - 1996	2.425	1.472	60,70%
1996 - 1997	2.499	1.475	59,00%
1984 - 1997	22.268	12.745	57,20%

Source: Boletín Informativo- Las Micosis en Venezuela (3).
Table 1. Percent of mycologically confirmed diagnoses of clinically diagnosed cutaneous mycoses in Venezuela (1984-1997).

A summary of reported cases by the main groups of mycologists in Venezuela between 1984 and 1997 are displayed on Table 2. Fifty seven percent were dermatomycoses; 25 percent, pityriasis; 19 percent, candidiasis; and only about 2 percent gather otomycosis, onychomycosis, tinea and piedra.

Group of Mycologists	Der	Can	Pit	Oto	Ony	Tin	Pie	Total
Instituto de Biomedicina, Caracas Instituto de Medicina Tropical, Sección Micología, Caracas. Hospital Universitario de Caracas, Laboratorio de Micología.	2.427	617	687	13	5	6	-	3.755
Universidad Nacional Experimental “Francisco de Miranda”, Coro.	995	226	698	6	55	-	-	1.980
Hospital Universitario, Maracaibo.	1.312	423	246	21	19	8	2	2.031
Hospital de Bárbula, Valencia.	770	224	227	5	3	2	-	1.231
Hospital “Manuel Núñez Tovar”, Maturín.	367	56	-	-	19	-	2	444
Instituto Autónomo Hospital Universitario de Los Andes, Mérida.	86	21	71	-	-	-	-	178
Hospital Central “Antonio María Pineda”, Barquisimeto.	880	405	737	40	1	2	1	2.066
Hospital Central “Antonio María Alcalá”, Cumaná-	922	379	572	-	-	-	-	1.873
Hospital Central de Bolívar.	272	66	283	-	13	-	-	634
Hospital Central de San Cristóbal.	122	7	26	-	-	-	-	155
Total	8.153	2.424	3.547	85	115	18	5	14.347

Der: Dermatophytosis; Can: Candidiasis; Pit: Pityriasis; Oto: Otomycosis; Ony: Onycomycosis; Tin: Tinea nigra; Pie: Piedra.
Source: Working Groups on Medical Mycology. Boletín Informativo- Las Micosis en Venezuela, 1-32 (3).
Table 2. Number of reported cases of human cutaneous mycotic infections by groups of work by geographical areas and type of mycoses. All Venezuela (1984-1997).

Relevant Papers on Human Systemic and Localized Deep Mycoses in Venezuela

Introduction

Table 3 displays a summary of reported cases of the fourteen human types of deep and localized mycoses published by several groups of researchers in Venezuela (1984-1997). We categorize these mycoses in four groups:

(1) Relatively common endemic mycotic diseases: paracoccidioidosis, histoplasmosis, chromomycosis, candidiasis and sporotrichosis, which add up 89.5%.

(2) Endemic mycotic infections but clinically less common diseases: cryptococcosis, coccidioidomycosis and eumycetomas, which add up 6.2%.

(3) Opportunistic mycotic diseases, which appear in patients suffering diabetes, cancer, or being treated with immunossuppressors, receiving long lasting venous perfusions (specially in intensive care units or organ transplants centers). Also opportunistic mycoses are associated to AIDS. Most common opportunistic mycoses are: aspergillosis, hypomycosis, zygomycosis, fusarium, and torulopsis, systemic candidiasis (not included in Table 2), wich add up about 4.3%.

(4) Very rare reported deep mycoses infections are rhinosporidiosis, and lobomycosis (not included in Table 3).

The above categorized human mycoses can be regrouped as follows:

(1) Systemic deep mycoses as shown in Map 1 are: (a) histoplasmosis, (b) paracoccidioidomycosis, (c) aspergillosis, (d) cryptococcosis, and (e) coccidioidomycosis (2).

(2) Localized deep mycoses as showed in Map 2 are: (a) chromomycosis, (b) sporotrichosis, (c) eumycetoma, (d) rhinosporidiosis, and (e) lobomycosis.

(3) Opportunistic mycoses: (a) aspergillosis, (b) candidiasis, (c) torulosis, (d) hypomycosis, (e) zygomycosis, (f) mucormycosis, and (g) fusarium. These opportunistic mycoses can produce either localized or deep mycoses, and they have eventually been published as case reports (2).

The etiologic agent of chromomycosis, Cladosporium carrionii, is found in the dry regions with xerophytic vegetation (States of Falcón, Lara and Zulia). Histoplasmosis (Histoplasma capsulatum), paracoccidioidosis (Paracoccidioides brasiliensis) and cryptococcosis (Cryptococcus neoformans) are found in the subtropical and templates Venezuelan regions as the Andes mountain system (States of Táchira, Mérida and Trujillo), Sierra de San Luis (States of Falcón and Lara), Cordillera de la Costa (States of Carabobo, Aragua, Miranda, Distrito Federal, Anzoátegui, Sucre, and Monagas), and Macizo Guayanés (State of Bolívar).

Group of mycologists	Par	His	Cry	Coc	Asp	Muc	Eum	Zyg	Chr	Spo	Can	Hyp	Tor	Fus	Total
Caracas´Mycology Laboratories.	337	191	20	1	7	1	9	1	6	68	91	4	2	-	738
Universidad Nacional Experimental. “Francisco de Miranda”, Coro.	21	13	1	9	4	-	4	-	293	1	13	-	-	-	359
Hospital Universitario, Maracaibo.	18	106	15	16	23	-	8	4	35	7	38	2	-	3	270
Hospital de Bárbula, Valencia.	98	23	4	-	7	1	2	-	5	4	7	-	-	-	150
Hospital “Manuel Núñez Tovar”,Maturín.	71	81	6	-	23	-	3	-	7	4	82	-	-	2	279
Hospital Central “Antonio María Pineda”, Barquisimeto.	32	23	1	15	1	-	3	-	24	9	4	-	-	-	112
Hospital Central “Antonio María Alcalá”, Cumaná.	23	3	1	-	1	-	-	-	-	3	4	-	-	-	35
Hospital Central de Bolívar.	15	1	2	-	-	-	-	-	-	22	20	-	-	-	61
Hospital Central de San Cristóbal.	10	3	5	-	-	1	-	-	-	2	6	-	-	-	26
Total	625	444	55	41	66	3	29	5	370	114	265	6	2	5	2.030

Par: Paracocidioidomycosis; His: Histoplasmosis; Cry: Cryptococcosis; Coc: Coccidioidomycosis;Asp: Aspergillosis; Muc: Mucormycosis; Eum: Eumycetoma; Zyg: Zygomycosis: Chr: Chromomycosis;
Spo: Sporotrichosis; Can: Candidiasis; Hyp: Hypomycosis; Tor: Torulopsis; Fus: Fusarium. Source: Working Groups on Medical Mycology. Boletín Informativo- Las Micosis en Venezuela, 1-32 (3).
Table 3. Summary of reported cases of deep human mycotic infections by working F research, geographical area and type of mycoses. All Venezuela (1984-1997).

Paracoccidioidomycosis (ICD-9 116.1; ICD-10 B41)

The control of Communicable Diseases Manual (CCDM) defines paracoccidioidomycosis as "a serious and at times fatal chronic (also known as adult type) mycosis characterized by patchy pulmonary infiltrates and/or ulcerative lesions of the mucosa (oral, nasal, GI) and of the skin. Lymphadenopathy is frequent. In disseminated cases all viscera may be affected; adrenal glands are especially susceptible. The juvenile (acute form), which is less common, is characterized by reticuloendothelial system involvement and bone marrow dysfunction" (4).

Pioneer studies on paracoccidioidomycosis (South American blastomicosis, paracoccidioidal granuloma) in Venezuela were carried by O'Daly (5). Reports of cases were published by D. R. Iriarte & C. Rodríguez (6), D. R. Iriarte (7), D. Guerra (8), A. Celis-Pé rez (9), A. Angulo-Ortega (10), J. Barros-Saint Pasteur (11), H. Benaím-Pinto (12), J. Baldó (13), F. Moncada-Reyes et al (14), and R. Avendaño-Monzón (15). Studies on pathology of paracoccidioidomycosis have been published by Mendelovici et al on ecology (16), Salfelder et al focused on animal model (17) and on reviews or chapters in books (18-20).

From 1993 to 2000 the following papers were indexed:

o G. San Blas, in 1993, published a review on Paracoccidioides brasiliensis, as the causal agent of a systemic mycosis highly prevalent in Latin America (Brazil, Colombia, Venezuela and Argentina). She summarizes the known clinical syndromes, pathological methods of diagnosis, immunology aspects (serological, humoral and cellular immunity and HLA antigen). Also agent virulence, antibiotic therapy, laboratory methods, and biochemical aspects of this fungus were included (21).

o Due to the endemic character of paracoccidioidosis in South America, multidisciplinary teams of researchers have gathered seven international meetings (three in Brazil, and the remaining in Colombia, Venezuela, Argentina, and Uruguay) (22).

o M. B. de Albornoz & R. Albornoz carried out an epidemiologic survey on paracoccocidioidosis tests looking for sensitivity of intradermo reaction results among groups of people from endemic area in Venezuela (23).

Histoplasmosis (American histoplasmosis) (ICD-9 115.0; ICD-10 B39.4)

The CCD Manual stresses that "two clinically different mycoses have been designated as histoplasmosis because the pathogens that cause them cannot be distinguished morphologically when growing on culture media as moulds" (4).

Let's refer only to the American histoplasmosis in this paper. In Venezuela, H. Campíns wrote two papers on histoplasmosis in 1953 (24, 25). The pioneer investigator on ecology of histoplasmosis, C. Capretti et al in 1963 isolated H. capsulatum (26). Salfelder continued the ecologic search of H. capsulatum in Mérida 1966 (27). Clinical and histopathologic descriptions of histoplasmosis were published by Salfelder et al between 1960 and 1967 (28-48). Experimental models were carried out by Salfelder et al in chickens (49), in mice (50-52), in hamsters (53-57), and dogs (58, 59). Books and chapters in books by Salfelder et al were published on clinical and histopathologic aspects (60, 61), and in atlas textbooks (62, 63) about histoplasmosis.

D. Borelli isolated H. capsulatum in Caracas (1957)(64), and Montemayor et al isolated it from 'Cavernas del Peñón' (Miranda State) in 1958(65), and Ajello et al, from Cueva del Guácharo (State of Monagas) also in 1960(66). Finally, M. Albornoz gathered data on specific skin sensitivity (intradermo reaction) in Paracotos (State of Miranda in 1971) (23). Among others, Angulo & Pollak published data on biopsies and autopsies on deep mycoses in 1990(67) and H Vargas-Montiel, on quantitative immunodiffusion techniques for monitoring deep mycoses in 1985 (68).

Coccidioidomycosis (Valley fever, San Joaquín fever, Desert fever, Desert rheumatism, Coccidioidal granuloma, Posadas disease) (ICD-9 114; ICD-10 B38).

The CCD Manual defines coccidioidomycosis as, "A deep mycosis that generally begins as a respiratory infection. The primary infection may be entirely asymptomatic or resemble an acute influenzal illness with fever, chills, cough and (rarely) pleuritic pain. About one fifth of clinically recognized cases (an estimated 5% of all primary infections) develop erythema nodosum, most frequently in Caucasian females and rarest in African-American males. Primary infection may heal completely without detectable residuals; may leave fibrosis, a pulmonary nodule that may or may not have calcified areas; leave a persistent thin-walled cavity or most rarely may progress to the disseminated form of the disease" (4).

In Venezuela, H. Campíns et al pub lished the first cases of coccidioidomycosis in 1949(69-70). Campins recognized coccidioidomycosis to be a public health problem in geographical areas where Coccidioides immitis is prevalent in the xerophytic and dry ecologic system in Western Venezuela (23). Zirit et al described an outbreak of coccidioidomycosis in Falcón State in 1959(72). G. Tapia isolated C. immitis from Venezuelan soils (Caracas) in 1969 (73). M. A. Quintero et al, in 1987, carried out a descriptive epidemiologic study in Pueblo Nuevo, Falcón State (74).

M. B. de Albornoz published a comprehensive review including definition, epidemiology (ecology), pathogenesis, clinical forms, laboratory diagnosis, pathology, and treatment updated up to 1996 (2).

The potential importance of coccidioidomycosis associated to several emergent syndromes was emphasized by M. Dolande et al in 1999, based on a series of cases (1994-1998). Looking for immunodiagnosis of deep mycoses among AIDS patients, they found that 64% were positive for histoplasmosis, but only 27% were HIV-positive for coccidioidomycosis (75). Further comments on AIDS associated mycologic syndromes will be made below.

Sporotrichosis (ICD-9 117.1; ICD-10 B14)

The CCD Manual defines sporotrichosis as: "A fungal disease, usually of the skin, often of an extremity, which begins as a nodule. As the nodule grows, lymphatics draining the area become firm and cord-like and form a series of nodules, which in turn may soften and ulcerate. Osteoarticular, pulmonary and disseminated multifocal infections are rare. Fatalities are uncommon. Laboratory confirmation is made by culture of a biopsy, pus or exudate. Organisms are rarely visualized by direct smear. Biopsies tissue should be examined with fungal stains" (4).

In Venezuela, M. Vegas, in 1935, described the lymphangitic syndrome of sporotricosis (76). In 1936, M. Jiménez-Rivero and L. Briceño-Iragorry published a series of 3 cases of Rhinocladiosis (Sporothrichum) schenkii (77). Other reports of cases and series of cases were published by S. Tálamo in 1946 (78), L. Montemayor in 1957 (79), and D. Borelli in 1963 (80). M. B. de Albornoz et al identified the antigenic structure of S. schenckii in 1980 (81). Clinical aspects of sporotrichosis were published by M. B. de Albornoz et al in 1989. These authors concluded that sporotrichosis infection is fairly common in endemic and non-endemic geographical areas in Venezuela (82).

In addition, L. Aristimuño and Y. López described the geographical distribution of S. schenckii and suggested that its mycelial form is able to be adapted to different ecological conditions, being the most important requirement for its growth the high environmental humidity (83). Also L. Aristimuño and Y. López surveyed a rural population applying the sporotrichina intradermal reaction and found 8.5% seropositive prevalence of infection among asymptomatic to clinical sporotrichosis. Among seropositive people, two-third have had some kind of clinical syndromes (83). The authors emphasize that one of the main risk factors to become positive to sporotrichosis infection is the agricultural occupation (83). M. Mendoza et al in 1992, using acrilamide gel and immunoblot techniques further characterized the metabolic antigen of filamentose form of S. schenckii (84). M. B. C. de Albornoz reported 87 cases of sporotrichosis in children (1956-1996) stressing that 37/87 (43.5%) appears like the cutaneous limphangitic form; 33/87 (38%) were localized nodules, and the other 17/87 (19.5%) were lymphatic form (cordon-like form)(84). M. B. de Albornoz concludes that sporotrichosis is the most frequent localized deep mycoses infection in Venezuelan childrens (85).

Chromomycosis (Chromoblastomycosis, Dermatitis verrucosa) (ICD-9 117.2; ICD-10 B43)

The CCCD Manual defines chromomycosis as: "A chronic spreading mycosis of the skin and subcutaneous tissues, usually of a lower extremity. Progression to contiguous tissues is slow, over a period of years, with eventual large verrucous or even cauliflower-like masses and lymphatic stasis. Rarely a cause of death. Microscopic examination of scrapings or biopsies from lesions reveals characteristic large, brown, thick walled, rounded cells that divide by fission in two planes. Confirmation of the diagnosis should be made by biopsy and attempted cultures of the fungus" (4).

O'Daly was the pioneer pathologist who observed the first cases of chromomycosis in Venezuela in 1937 and 1938, published in 1943 (86). He isolated a not yet classified etiologic agent from soils of dry geographic zones in 1943. Lately this agent was classified by Trejos as Cladosporium carrionii in 1954 (87). Fonsecaea pedrosoi is the etiologic agent of chromycosis in other climatic areas. Richard Yegres et al, until 1992, had diagnosed 397 cases of chromomycosis in the Mycology Unit of Falcón State(88). The 'prevalence' of infection was 16/1000 persons in endemic areas (more frequent in adults and clustered in families) (88). In 1996, Pérez-Blanco et al published the first case of chromomycosis due to Rhinocladiella aquaspersa in Venezuela (89). Yegres et al's main contribution to improve the knowledge on endemic chromomycosis in Venezuela may be the search for epidemiologic aspects, which include occupational infection in goat shepherds (90), and the isolation of strains from xerophytic environments (91-93).

Mycetomas (ICD-9 039; ICD-10 B47)

The CCD Manual defines mycetoma as: "A clinical syndrome caused by a variety of aerobic actinomycetes (bacteria) and eumycetes (fungi), characterized by swelling and suppuration of subcutaneous tissues and formation of sinus tracts with visible granules in the pus draining from the sinus tracts. Lesions are usually on the foot or lower leg, sometimes on the hand, shoulder and back, and rarely at other sites. Mycetoma may be difficult to distinguish from chronic osteomyelitis and botryomycosis, the latter been a clinically and pathologically similar entity caused by a variety of bacteria, including staphylococci and gram-negative bacteria. Specific diagnosis depend on visualizing the granules in fresh preparation or histologic slides and isolation fungus in culture" (4).

Eumycetoma (Maduromycosis, Madura foot) (ICD-9 117.4; ICD-10 B47.0)

Eumycetoma is caused by Madurella mycetomatis, M. grisea, Pseudoallescheria (Petriellidium) boydii, Scedosporium (Monosporium) apiospermum, Exophiala (Philalophora) jeanselmei, Acremonium (Cephalosporium) recifei, Acremonium falciforme, Leptosphaeria senegalensis. Neotestudina rosatii, Pyrenochaeta romeroi, or several other species (4).

In Venezuela, mycetomas are either produced by 'true' fungi (eumycetomas) or by bacteriae actinomycetes (actinomycetomas). The most frequent etiologic eumycetoma agents in Venezuela are Madurella grisea, Pyrenochaeta mackinonnii, and P. romeroi (94-96). A summary of etiologic agents of eumycetoma in the State of Lara is displayed in Table 4 (95).

Etiologic agent	Number of cases	Percent
Pyrenochaeta mackinonnii	8	32,00%
Pyrenochaeta romeroi	6	24,00%
Madurella grisea	5	20,00%
Pseudochaetosphaeronema larense	1	4,00%
Phomapyllosticta	1	4,00%
Fusarium falciformis	1	4,00%
Moho aleuriosporado	1	4,00%
No precisado	2	8,00%
Total	25	100,00%

Source: Serrano, Mejía (94) (updated 2000).
Tabla 4. Etiologic agents of eumycetoma in Lara State, Venezuela (1966-1998).

Actinomadura madurae is the most common agent of actinomycetoma in Venezuela, followed by Nocardia brasiliensis, and N. asteroides. Table 5 displays the geographical distribution of reported cases of actinomycetoma by states in Venezuela, by main etiologic agents In the State of Lara were reported 35/59 (59%) and Actinomadura 17/59 (37%) of the reported cases in Venezuela (94). Novoa-Montero and Serrano inference is that either eu or actinomycetomas are not a public health problem in Venezuela (97). This fungi human mycoses (eumycetomas) produce endemic infection, but prevalence of clinical cases appears to be very low. Mycetomas are associated to low and very low socioeconomic conditions, especially among agriculture and field workers in Falcón, Lara and Zulia states, where xerophytic and dry regions are extensive (98). The ratio between prevalence of infection and prevalence of clinical cases should be a matter of further research in order to also define how (pathogenic) and why (other risk factors as covariates) only quite a few people became clinically sick in rural communities where prevalence of seropositivity is high (97).

State	A. madurae	A. pelletieri	N. brasiliensis	N. asteroides	N. otitidiscaviarum	Nocardia sp.	S. somaliensis	Total
Aragua	1	-	-	-	-	-	-	1
Barinas	-	-	1	-	-	-	-	1
Falcón	2	-	2	-	-	2	-	6
Dtto. Federal	2	-	2	-	-	1	-	5
Lara	11	-	8	3	1	8	4	35
Mérida	-	-	1	-	-	-	-	1
Miranda	3	-	2	-	-	-	-	5
Yaracuy	1	-	1	-	-	-	-	2
Zulia	2	1	-	-	-	-	-	3
Total	22	1	17	3	1	11	4	59

Source: Serrano, J. A. (95) (updated 2000).
Table 5. Distribution of clinical cases of Actinomicetoma reported in Venezuela, by States of (1976-1998).

Candidiasis (ICD-9 112; ICD-10 B37)

The CCD Manual defines candidiasis as: "A mycosis usually confined to the superficial layers of skin or mucous membranes, that present clinically as oral thrush, intertrigo, vulvovaginitis, paronychia or onychomycosis. Ulcers or pseudo-membranes may be formed in the esophagus, stomach or intestine. Candidemia most commonly arises from intravascular catheters and may produce lesions in many organs, such as kidney, spleen, lung, liver, eye, meninges, brain and native cardiac valves or around prosthetic cardiac valves" (4).

In Venezuela, candidiasis, candidosis, candidomycosis, previously known an moniliasis, was firstly reported in 1921 by E. González associated to bronchial moniliasis (99). P. Guerra, in 1935, wrote his pioneer dissertation on the rol of pathogenic yeast on dermatology (100). He and M. Langeron published a description on C. stellatoidea in 1938 (101), and P. Guerra described "erosio interdigitalis" by Monilia albicans and clinically associated to eritrasma (102).

M. Feo carried out comprehensive studies on non-pathogenic and pathogenic yeasts in Venezuela (103, 104). S. Rodulfo and M. Mendoza clarified that C.albicans most common infection is associated to serotype A candidiasis (69%), while serotype B represents (31%) of infections confirmed by biopsy. Candidiasis serotype A is frequent as an emergent infection in patients with AIDS (105).

Lobo's Disease (Lobomycosis) (ICD-9; ICD-10 B48.0)

The CCD-Manual describes "Keloidal blastomycosis (Lobo disease), a disease with only skin involvement formerly confused with paracoccidioido mycosis, is caused by Loboi loboi, a fungus known only in its tissue form and not yet grown in culture" (4). Taborda et al renamed Lobo's Disease agent as Lacazia loboi to pay tribute to Carlos Da Silva Lacaz.

Jorge Lobo (Recife, Brazil) described the first case in 1949 (106). Campo de Aasen, in 1959, described the first case of Lobomycosis in Venezuela (107). Other reports of cases in Venezuela were published by F. Battistini in 1966 (108), and M. Vargas-Montiel in 1973 (109). Lobo's disease is mainly found in the Orinoco River basin and the Lake Maracaibo regions (109). Convit and other members of de 'Comisión para el estudio de las micosis en Venezuela' summarized data on mycetomas, chromomycosis, sporotrichosis and Lobomycosis. This Committee stated that by 1961 only two cases of Lobomycosis had been reported inVenezuela's Guayana (110). Ávila-Mayor et al, in 1985, reported a new case in Zulia State, confirmed biopsy (111).

Rhinosporidiosis (ICD-9 117.0; ICD-10 B48.1)

Rhinosporidiosis (Rhinosporidium seeberii) (112,113) is a granulomatous chronic infection, not transmissible man-to-man, characterized by polipoid lesions in man and some quadruped animals, chicks and gees (114). Local infections are mainly oral, nasopharinx, rectal and genital mycoses. Rarely, skin, bronchi and bones (114).

Rhinosporidiosis is endemic in Venezuela. It is mainly acquired when people are working in rice fields in Portuguesa and Barinas States. L. Potenza and A. Celis-Pérez described the first case in 1947 (115). Other case reports stressing conjuntival infection were published R. Sánchez-B. & M. Schargy, in 1947(116) and in 1953 (117). V. Alizo & F. Wenger in 1953 (118), F. Gómez et al in 1962 (119), and F. Gómez in 1966 (120).

E. G. Vogelsang described R. seeberi in an equine infection in Venezuela, in 1955 (121). Sauerteig published a series of 16 cases of rhinosporidiosis in children and young adults in 1985 (122). J. Montarroso observed 20 cases of ocular rhinosporidiosis, K. Brass observed other 10 cases of rhinosporidiosis along of 30 years activity in Carabobo State. Cases described by K.Brass came from Barinas and Portuguesa States in Venezuela (cited by E. Sauerteig, 122).

Oportunistic and Emergent Mycoses Infections in Venezuela

Main mycoses agents usually found worldwide.

Opportunist fungi currently are cosmopolitan infections within which etiologic species differ according to each geographical region. Table 3 displays that opportunistic mycoses infections described in Venezuela have been associated to Zygomycetes sp. (ICD-10 B46.0) and mucormycosis (ICD-10 B46.0; B46.5); Candida sp. (ICD-9 112; ICD-10 B37) which is the most frequently reported; less frequently reported are Aspergillum sp. (ICD-9 117.3; ICD-10 B44), and Fusarium sp.

The following opportunistic infection agents are mainly associated to the so called emergent mycotic syndromes: Cryptococcus neoformans (ICD-9 117.5; ICD-10 B43), Histoplasma capsulatum (ICD-9 115.0; ICD-10 B39.4), Coccidioides immitis (ICD-9 114; ICD-10 B38), Paracoccidioides brasiliensis (ICD-9 116.1; ICD-10 B41), and Pneumocystis carinii (ICD-9 136.3; ICD-10 B59) (4).

Mycotic emergent syndromes are associated to specific underlying diseases, specially to diabetes mellitus, leukosis, lymphomas, drug additions, AIDS, and to whatever other immunosuppressed individuals.

Emergent mycoses syndromes in AIDS patients in Venezuela

Venezuela is not the exception with respect to epidemics of deep and systemic mycoses associated with the increasing number of AIDS groups of patients, which is rocketing since 1989, when AIDS clearly showed to be a relatively common syndrome in this country.

Fernández and M. Mandells, in 1990, in a series of 490 patients (1988-1989) found 64 patients with emergent mycoses syndromes, among which 43 suffered deep mycoses (histoplasmosis, cryptococcosis, paracoccidioidosis), systemic candidiasis, and doubled infected by cryptococcosis and histoplasmosis (123).

M. Dolande et al, in 1999, checked up 740 immunologic samples analyses confirmed that 265 came from AIDS patients within whom 66 showed to be positive for the following systemic mycoses: 42 for histoplasmosis, 98 for cryptococcosis, 5 for paracoccidioidomycosis, and 1 for coccidioidomyco sis. The 475 samples taken from asymptomatic HIV positive patients appeared to be negative to systemic mycoses (124). Merheb-Guillot et al revised 404 autopsy protocols of immunosuppressed persons (1985-1989) (338 without HIV and, 66 HIV positive). Candida albicans was found in 49.2%, H. capsulatum in 41.3%, and Cryptococcus neoformans in 12.7% among free AIDS-free dead individuals. When AIDS dead individuals were checked up, histoplasmosis proportion was 18.4% (lower than among AIDS free dead), cryptococcosis proportion was 33.3% (higher than among AIDS free ones), meanwhile candidiasis was present in 23.2% (also lower than among AIDS free dead) (125).

I. Peña et al reported a patient biopsy of some Kaposi-like lesions, truly due to Cryptococcus neoformans (126). Santiago et al, in 1998, examined 346 AIDS patients (Central Venezuela); 124 samples (38.8%) had some kind of deep mycoses (C. neoformans, H. capsulatum, P. brasiliensis and C. albicans) (127).

A. Río-Fabra observed that the most frequent opportunist agent worldwide associated to AIDS is Pneumocystis carinii, meanwhile H. capsulatum, which mainly produces pulmonary acute infections in AIDS patients, is most frequent in Venezuela. C. neoformans, P. brasiliensis and C. immitis have been rarely seen among AIDS patients in Venezuela (128).

Relevant Venezuelan Contribution to Drug Treatment of Human Mycoses

The original relevant drug developed in Venezuela aimed to treat mycoses was patented by Apitz-Castro et al in 1987(129), after careful assays following his pioneer communication in 1963(130). This drug has been named 'ajoene' (E,Z,4,5,9 trithiadodeca-1,6,11-thriene 9-oxides) (131). It is an organosulphurate compound, originally obtained from the alcoholic extracts of garlic (130). This drug has both in vivo and in vitro antifungal activity for pathogenic fungi, say cutane ous (131) deep localized human mycoses, chromomycosis (132); paracoccidioidosis (133). Antimycotic effect of ajoene seems to be due to a selective inhibition of phosphatidylcholine biosynthesis in inferior eucaryotes (131).

Historical and Major Contribution of Venezuelan Physicians, Pathologists and Mycologists to Improve Mycology Knowledge.

Table 6 epitomizes the historical and major contributions of Venezuelan physicians, early pathologists and mycologists to consolidate mycology as a scientific discipline in Venezuela. This summary includes data from 1882 to 1999 (134-217).

No.	Author(s) name (date) and main medical field of work (reference)	Pioneer or main mycological contribution(s)	Type of mycoses	Venezuelan geografical region	Type of medical research	Comments
1.	De Armas, D. (1982) General physician (134)	First Venezuelan report on mycoses	Tinea tonsurans	Anzoátegui State	Clinical report	The very first pioneer on cuta-neous mycoses in Venezuela, and maybe in South America.
2.	Montiel-Pulgar, S. (1908) General physician (135)	First Venezuelan report on actinomycosis	Actinomycosis*	Zulia State	Clinical and epidemiological	The very first pioneer report on actinomycosis* in Venezuela.
3.	Fonseca, M. A. (136)	First review on humanactinomycosis	Actinomycosis*	North-CentralVenezuela	Review	The first monograph on actino-mycosis (to teach physicians).
4.	Rangel, R. (1909) Medical (137) Laboratory technician	Rangel observed a case of apparent association between cervico-facial epithelioma and actinomycosis*. Also he reported the very first non-published case of actinomy-cetoma	Actinomycosis* and epithelioma	Caracas	Clinical report, microbiological and histopatho-logical descrip-tion	The very first pathologic re-view study on actinomycosis.
5.	Medina-Jiménez, R. (1913) General physician -138	Review of “several mycotic diseases”	Cutaneous mycoses	Caracas	Clinical report	Historical importance. Paper on etiology of the clinical der- matophitosis.
6.	Pino-Pou, R. (1917) -139	First clinical report on eumycetoma	Deep mycosis	Caracas	Clinical report	A meta analysis by D. Borelli concluded that this case was probably a Buffardi´s myceto-ma due to Aspergillus buffardi.
7.	González, E. (1921) General physician (99)	Clinical and microbiological observations of a bronchialmoniliasis	Deep mycosis	Caracas	Clinical and microbiologic report	This was the first report on moniliasis (candidiasis) and the first Venezuelan case report of Candida tropicalis.
8.	Iriarte, J. and González, E. -1921 General physicians (6, 7)	The authors described as “blastomycosis” a syndrome with some pathology that probably was a deep mycosis	Deep mycosis	Caracas	Clinical and microbiologic report	Pathology probably caused by yeast.
9.	Jiménez, B. and Cuenca, M. -1923 General physicians (140)	Report of a case of human actynomycosis*	Deep mycosis	Zulia State	Clinical and microbiologic report	The first report on actinomy- cosis* in Western Venezuela.
10.	De Bellard, E. P. (1924) General physician (141)	Report of a case of human actynomycosis*	Deep mycosis	Caracas	Clinical and microbiologic report	The first case report of actino-mycetoma (since Rangel´s case was only mentioned by Rísquez, published in 1929).
11.	Rísquez, J. R. (1929)Internist M. D. (142)	Monography on general mycology lectures for medical students	Cutaneous and deep mycoses	Caracas	Clinical and histopathologi-cal report	Rísquez includes unpublished data by Rangel Briceño, Iragorry and Villalobos.
12.	Del Corral, P. (1934) General physician (143)	First Venezuelan report on hair mycosis by Trichosporum ve-nezuelensis (Piedraia hortai)	Hair mycosis	Aragua State	Clinical and microbiologic report	Hair mycosis is relatively uncommon.
13.	Vegas, M. (1935) Dermatologist (76)	First case report on sporotrichosis in Venezuela	Cutaneous mucose mycosis	Caracas	Clinical and histopathologi-cal report	M. Vegas is the protoderma-tologist in Venezuela.
14.	O’Daly, J. A. (1937) Pathologist (5) -1943	He reported the first case of chromomycosis in Venezuela (1947). In 1943 O’Daly isola-ted the ethiologic agent of chro-momycosis from Opuntias as Cladosporium carrionii. This agent was lately classified by Trejos as Cladosporium carrionii (1953). In addition, O’Daly reported the first case of Paracoccidioides brasilien-sis in Venezuela.	Deep mycosis	Caracas	Clinical and histopathologi-cal report	J. O’Daly was a pioneer on pathological studies of humanmycoses in Venezuela.
15.	Iriarte, D. R. and Rodríguez, C. (1939)-1928 General physicians (6, 7)	Case-reports which support O’Daly’s finding of P. brasi-liensis in Venezuela	Deep mycosis	Caracas	Clinical and histopathologi- cal reports	Both O’Daly’s and Iriarte and Rodríguez papers stem for subsequent studies on P. brasiliensis in Venezuela.
16.	Guerra, P. (1935) (1939) Dermatologist (1949) Pathologist and Internist (100, 102)	First studies on human patho-genic yeast (Candida) in Venezuela. Founder of the National Medical Mycology Laboratory	Cutaneous-mucose	Caracas	Clinical and microbiologic report	It is a very relevant contribu-tion of medical pathologists to mycotic human infections in Venezuela.
17.	Potenza, L. and Pérez Celis, A. (1947) Pathologist, Othorrinolaryngologist -115	These authors described the first Venezuelan case of rhinosporidiosis	Deep mycosis	Caracas	Histopatologic report	It is a very relevant contribu-bution of medical pathologists to the knoledge of human rhinosporidiosis in Venezuela.
18.	Montemayor, L. (1943) Medical Lab- Technologist, Mycologist (79)	Montemayor continued the pioneer work of P. Guerra after having been Guerra’s technician. Since 1944 he cul-tured many fungi and taught Mycology at The Central Uni-versity. Also he was chairman and chief of the Laboratory of Mycology of the National Institute of Hygiene in Venezuela	Cutaneous, airborne mycosis and deep mycosis	Caracas	Laboratory diagnosis of human mycoses	His reference laboratory sup-ported the organization of teaching mycological medical diagnosis of mycosis. He is the first mycologist in Venezuela
19.	Angulo-Ortega, A. (1948) Pathologist (10)	Pioneer study of pulmonary mycotic infections in Vene-zuela (Histoplasmosis, cryp-tococcosis, paracoccidioido-sis, coccidioidosis and nocardiosis)	Deep mycoses	Caracas	Review	This study allowed to define the boundaries of pulmonary tuberculosis and pulmonary mycoses when anti-TBC triple drug did not heal patients.
20.	Potenza, L. and Benaim-Pinto, H. Pathologist/Internist -144	They described the first central nervous system infection by Cryptococcus neoformans detected in Venezuela	Deep mycosis	Caracas	Clinical and histopatologic report	This was the first case-report of a mycosis later known to be a worldwide endemic disease described in Brasil in 1941 (cryptococcosis).
21.	Campíns, H. (1949) -1953 Dermatologist (24, 25)	The author reported series of cases of the coccidioido-mycosis (1949) (71) and histoplasmosis in Venezuela (1950) (25)	Deep mycosis	Caracas	Clinical mico-logic and intradermo reaction reports and others	First report of cryptococcosis lately known as worldwide endemic mycoses.
22.	Pollak, L. (1953) Microbiologist (145)	This microbiologist succeeded to isolate H. capsulatum in Venezuela -1953	Deep mycosis	Caracas	Review	This study opened the door to further research on histoplas-mosis in Venezuela.
23.	Brass, K.; Polo, F. and Montemayor, L. (1954) Pahologist/Clinical/ Mycologists (146)	This multidisciplinary team clinically, pathologically and mycologically defined the first human case by Blastomy-ces dermatitidis (North Ame-rican Blastomycosis) in Venezuela	Deep mycosis	Caracas	Case report	First finding of an “exotic” deep mycosis in South America.
24.	Borelli, D. (1954-1992) Dermatologist Mycologist (147-149)	Borelli has carried out iso-lation and characterization of more than ten human patho-genic fungi species in Vene-zuela and wrote many papers on research works on ecology, biology, pathogenicity of mycoses. Also he introduced several techniques and media for fungi	Cutaneous mucose, deep mycoses	All Venezuela	Clinical, ecolo-gical, laboratory diagnosis, teaching Myco-logy, therapeutic trials, host-para-site relationship or several micoses	Dante Borelli is the landmark on the development of mycologic studies in Vene-zuela during 50 years.
25.	Maekelt, G. (1961) Immunologist (151, 152)	Founder of the first Venezue-lan laboratory for serologic diagnoses of human mycoses (Tropical Medicine Institute)	Deep mycoses	Caracas and all Venezuela	Seroepidemio-logy, Laboratory tests	Maekelt is the pioneer on the development serodiagnosis of deep mycoses to carry out community surveys and field work in epidemiologic studies.
26.	Campo de Aasem, I. -1959 Dermatologist (107)	She described the first case of blastomicosis queloidiana (Lobo’s mycosis)	Deep mycosis	Caracas	Clinical and histopatholo-gical report	First case reported in Venezue-la of this Amazon Basin ende-mic disease found by J. Lobo in Brasil in 1931.
27.	Carbonell, L. (1964) Pathologist (153, 154)	Pioneer investigator in ultra structural and cytochemical studies on human deep myco-ses etiology agents (mainly paracoccidioidosis and histoplasmosis)	Deep mycoses	Caracas	Cell and mole-cular biology report	Pioneer in multidisciplinary studies on human pathogenic fungi (Kanetsucna, Rodríguez, Cunto de San Blas).
28.	San-Blas, G. and San-Blas, F. (1968) Chemist and Biologist -133	The San Blas couple deve-loped genetic, chemical, cyto-chemical and molecular studies of P. brasiliensis and other deep mycoses fungi	Deep mycoses	Caracas	Cell and mole-cular biology	These researchers started and maintain the new frontiers between the cell and molecu-lar biologic aspects of human pathologic fungi.
29.	Serrano, J. A. (1969-2000) Mycologist Microbiologist (94, 97)	Serrano is a pioneer in the ultrastructural and cytoche-mistry of eumycetoma and its etiologic agents in Vene-zuela (among other studies)	Deep mycoses	Mérida/Lara States	Cell biology host parasite relationship and ultrastruc-tural studies	Serrano founded the electron mycroscopic research Labora-tory in the University of The Andes in Mérida, Venezuela.
30.	Yegres, F. and Richard-Yegres, N. (1985-1989) Biologist and Mycologist (90, 93)	The Yegres couple showed chromomycosis is an ende-mic fungi infection and disease in Northwestern Venezuela. Also they develo-ped ecological and lab tech-nical methods for fungi iso-lation and characterization from natural environments (Cladosporium carionii and Phialophora verrucosa Fonsecaea pedrosoi)	Deep mycoses	Falcón State	Mycological cell biology, ecology and laboratory techniques (Se-veral reporteds)	This couple of investigators conducted multidisciplinary studies on chromomycosis in Falcón State, Venezuela.
31.	Romero, H.Biotechnologist (MSc)Mycologist (PhD)(155-157)	H. Romero’s main contribu-tion to Mycology is produc-tion of antigens to develop sero- and immuno-diagnos-tic method for eumycetomaand chromomycosis. Theseantigens are aimed to developboth clinical diagnosis, com-munity-based epidemiologicsurveys, or case-control studies	Deep mycoses	Caracas	Sera and immu-ne diagnoses ofeumycetoma andchromomycoses	Romero was a novel well-trainee mycologist underguidance of or Mackenzie(London).
32.	Novoa-Montero, D.(1994-1999) chronicdiseases epidemiologist(1, 158, 159, 161, 165,174)	This author has proposed amultidisciplinary biomedicalfamily-case comparison epidemiologic model tostudy asymptomatic or symp-tomatic infection by eumyce-tes (environment-to-man trans-mitted mycological infection).This model is also valid tostudy any other environment-to-man transmitted infection.	Deep mycoses	Mérida	Multidisciplinarybasic science methodology joined to empiricand standard epidemiologies	This epidemiologic and mul-tidisciplinary method of studyis openig the door to study worldwide deep mycoses be-yond further than case-report,series of cases, pathologicalobservations, in ordermake inferences to improveregional, national or inter-national public healthmeasures.
* This table includes case reports on actinomycosis as “actinomycetomas” among mycoses, since when published, the etiologic agents of mycetomas had not yet been split in actinomycetoma (bacteria) and eumycetoma (fungi).

Table 6. Historical and major contributions of Venezuelan physicians, pathologists and mycologists (1882-1999).

In 1882, D. de-Armas described the first case of tinea tonsurans in Venezuela (134). Turning the XIX century appeared the so called 'Renaissance of the Venezuelan Medicine' The medical leaders of that 'renaissance' were F. A. Rísquez (1856-1941), L. Razetti (1862-1932), José Gregorio Hernández (1864-1919), and J. Santos-Dominici (1869-1954). As a matter of fact, Razetti and Dominici, while being trained in France, conceived a specific proposal to carry out a new approach to develop medical sciences in Venezuela during the beginning of XX Century. This 'renaissance' included, among other objectives which were reached indeed: (a) Foundation of the Hospital Vargas (Caracas, 1891); (b) foundation of the Department of Histology, Pathology Experimental, Physiology and Bacteriology (1891); (c) creation of the Journal Gaceta Médica de Caracas (1893); (d) foundation of the Pasteur Institute of Caracas (1895); and (e) foundation of the Laboratory of the Hospital Vargas (1902) (162).

Based on the activity of the above mentioned institutions, several Venezuelan professionals published reports of clinical cases of mycoses. They were S. Montiel-Pulgar in 1908 (135), M. A. Fonseca (136), R. Rangel in 1909 (137), R. Medina-Jiménez in 1913 (138), R. Pino-Pou in 1917 (139), E. González in 1921(99). B. Jiménez and M. Cuenca in 1923 (140), and E.P. De Bellard in 1924 (141).

J. R. Rísquez (1883-1947) succeeded J. Gregorio Hernández (died in 1919) in the Cátedra de Bacteriología y Parasitología (162). In addition to important investigations on parasitology and bacteriology, he wrote a paper on pie de Madura in 1927 (142). J. R. Rísquez excited his students to carry on research on Venezuelan infectious diseases. Among his undergraduate medical students, L. Briceño-Iragorry and H. Villalobos wrote a paper on Actinomycetoma in 1927 (142).

Del Corral in 1934 (143), and M. Vegas in 1935 (76) reported cases of hair and cutaneous mycoses. Also J. A. O'Daly in 1937 (5) and D. R. Iriarte Rodríguez in 1939 (6) reported cases on deep mycoses.

By 1937, a new medical pioneer, P. Guerra (1903-1944), went back to Venezuela after having been trained as post graduate fellow by Paul Ravaut and M. Langeron in Paris. Guerra and Langeron published the description and identification of Candida guilliermondii (100). They also carried out studies on Candida stellatoidea (101). Guerra was chairman of the Unit of Dermatology and Pathology of the Hospital Vargas in Caracas. His relevant contribution to the study of mycoses in Venezuela is related to pathogenic yeasts (100). He was the founder of the first Venezuelan Laboratory for diagnosis of human mycoses (162). Potenza and Pérez-Celis described the first case of rhinosporidiosis in Venezuela in 1947 (115).

In 1943, Lorenzo de Montemayor assumed as assistant technician of Dr. Guerra. He evolved to become a technologist at the Universidad Central de Venezuela in 1963, and was a post graduate student of J. Mackinnon, in Montevideo (Uruguay) (164). Lately he went to California (USA) to continue his training in mycology. Thereafter, he was named Professor of the Escuela de Bioanálisis (Universidad Central de Venezuela) where he trained many laboratory medical technologists (164). One of Montemayor's paper on mycology was his description of Favus aviari in 1946 (163). Montemayor's main contribution to mycologic studies was to maintain and increase a pathogenic fungi collection in Caracas as well as to improve training and teaching on mycology in Venezuelan Universities (164).

Between 1946 and 1975, E. Tejera sampled many Venezuela's and other countries' soils. Tejera colleted 22,750 samples from the natural environment. He isolated 32,499 strains of bacteria or fungi among which many were actinomycetes. Tejera also isolated some antibiotics; for example the Streptomy ces venezuelae, producer of chloramphenicol and 'mycobaccidina', one of the active antibiotics against Pseudomona sp. We consider E. Tejera to be the Venezuelan pioneer of ecological studies on fungi (165, 166).

Potenza and Benaím-Pinto described the first case of central nervous system infection by Cryptococcus neoformans (144).

In central western Venezuela, Dr. H. Campíns, dermatologist and mycologist, founded in 1953 the Department of Dermatology at the Hospital Central Antonio María Pineda in Barquisimeto, Lara State. He is a pioneer investigator on deep mycoses, specifically on coccidioidomycosis (69). Campíns trained the first group of dermatologist-mycologists in central western Venezuela, (Segundo Barroeta, María Antonieta Mejía, Ramón Zamora, among others). The Department of Dermatology in Barquisimeto was named after H. Campíns, as a tribute to his memory and acknowledgment to his outstanding activity. Nowadays, the unique Master Degree in Dermatopathology held in Venezuela is sponsored by this department.

By the fifties of the XX Century, the following pioneer mycologists published sound papers. L. Pollak in 1953 on histoplasmosis (145), K. Brass et al, in 1954, on blastomicosis (146), D. Borelli on new pathogenic fungi species 1955 (147-150); and G. Maekelt who developed seroepidemiologyc tests to be applied to diagnose clinical patients and to validate descriptive epidemiologic studies (151, 152).

In Zulia State, J. Hómez-Chacín founded the Department of Dermatology and the Unit of Parasitology and Tropical Medicine at the School of Medicine, Universidad del Zulia, in 1954. In addition, G. Casas-Rincón and J. Hómez-Chacín founded the Section of Medical Mycology in the Department of Microbiology at the same University in 1971. By 1957, a Venezuela Governmental Steering Committee, named Comisión Coordinadora del Estudio Nacional de las Micosis was led by J. I. Baldó. Its objectives were aimed to increase the state of the re search and cumulative knowledge on human mycoses in Venezuela. This committee made a review on the contemporary Venezuelan knowledge on mycoses. A synthesis of this group of mycologists' papers was presented on the IV Congreso Venezolano de Tisiología y Neumonología, Valencia (Ven.) Oct 9-12, 1959. In 1961, Mycopathologia et Mycologia Applicatada (T. Benedek, editor) published its Proceedings (167). Fruits of that Comisión were the First Venezuelan Workshop in Mycology (168), and a monograph, 'Cartilla Micológica' (169). In the sixties of XX Century, in Venezuela, the known cases of mycoses were on histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, blastomicosis, mycetomas, candidasis, cryptococcosis, chromomycosis, sporotrichosis, nocardiosis, actinomycosis, rhinosporidiosis, and cutaneous mycoses (162). This Comisión ceased its activities by 1979 (170).

Other important investigations on mycoses in Venezuela are the papers from the Venezuelan pathologists I. Campo de Aasem on blastomycosis queloidiana (Lobomycosis) in 1957 (107), L. Carbonell on ultrastructure and cytochemistry of deep mycoses agents (153-154, 171), G. de San Blas and F. San made sound contributions on molecular biology of P.brasiliensis and other deep mycoses (21, 133).

M. B. de Albornoz, after her training as a fellow in Mycology at London School of Hygiene and Tropical Medicine, became the leader of a group of mycologists now-a-days spread along Venezuela (Caracas, and the States of Bolívar, Falcón, Monagas, Táchira, Zulia, Barinas, Carabobo, Lara y Sucre) (2). This mycology group of research on mycoses main achievements have been: (a) Standardization of methods for serological, immunological, skin tests…; (b) validation of such methods; (c) application of validated tests for developing community surveys, and to carry out clinical and laboratory tests; (d) promotion and development of multidisciplinary and interdisciplinary groups for diagnosis, research and teaching in Mycology; (e) application of research on Mycology pointing out to solve specific problems or to promote a better public health applications in selected Venezuelan communities (3).

Doctor M. B. de Albornoz's and her group of mycologists have published 32 issues of the Boletín Informativo: Micosis in Venezuela between 1985 and 1998, and it will continue to be published. This 'boletín' has included many aspects of several Venezuelan human mycoses: (a) reports of important cases or several series of cases; (b) laboratory methods on Mycology; (c) descriptive epidemiologic data; (d) therapeutic trials; (e) biographical sketches of relevant Venezuelan mycologists, etc. (3). Dr. Albornoz's team work on editing, publishing and keep-on-going this boletín, supported by their own financial resources and sporadic private pharmaceutical companies subsides, are worth to be though over as the best contemporary academic effort to improve Mycology in Venezuela as a new scientific discipline among the Biology Sciences.

Recently, in 1996, M. B. Albornoz edited a handbook entitled, 'Temas de Micología Médica' (2). This handbook includes the most recent concepts and advances on Medical Mycology. It is an updated handbook, which is very useful to introduce Spanish speaking students and professionals interested on the field of human medical mycology (2). Dr. Albornoz and her team activities on mycology in Venezuela was worth enough to deserve the creation of the Mycologic Section at the Annual Meeting of the Venezuelan Association for the Advancement of Sciences (AsoVAC).

New advances on mycology research sero/and immunodiagnosis of eumycetoma and chromomycosis were the outstanding contributions on immunology and serodiagnoses of eumycetoma and chromoblastomycosis published by H. Romero (1989-1999) (155-157).

Between 1991 and 1994, Dr Fanny Arreaza and Ms Gladys Tapia taught four courses of Medical Mycology for physicians, medical technologists, and biologists. These courses were sponsored by the Venezuela Ministry of Health (2, 172).

In the field of teaching Mycology as an advanced discipline, J. A. Serrano published two papers on ultrastructural and cytochemical aspects of actino of eumycetes and mycetoma (95, 173). In addition, F. Yegres and N. Richard-Yegres have sponsored four post graduate courses on Medical Mycology in the School of Experimental Medicine at the University 'Francisco de Miranda', Coro, Falcón State, between 1994 and 1999. These post graduate courses have been cosponsored by the Venezuelan National Institute of Hygiene. This course involved to be a Master Degree in Medical Mycology in 1999.

Since 1994 D. Novoa-Montero, chronic diseases epidemiologist, has been inviting mycologists to follow a new approach to evolve their researches on deep mycoses. His proposal has been called "multidisciplinary family-case comparison epidemiologic model", which is a practical and effective application of the clinical epidemiology discipline, based on the so called empirical epidemiology. Figure 1 displays Novoa-Montero proposal as a flow chart to carry out productive research on man-to-man transmitted mycoses (and, for extension, some bacterial chronic infections and diseases). This submodel of case-control epidemiologic design has been proposed at several international symposia on Mycology, as in Moscow (Russia), in 1994 (1), in Jabalpur (India) in 1996 (158), in Beijing (China) in 1997 (159), and in Davis (California) at SILCIBIO 2000 (174). Related papers resulting from these symposia have been published in Biotechnology, Russia (1), and in the Journal of Medical Mycology, France (97), and in the Boletín de la Sociedad Venezolana de Microbiología (161).

Textbooks and Monographs on Mycoses or Mycology in Venezuela

We could trace the following books:

(1) Cartilla Micológica. This monograph was edited by Fundación Eugenio Mendoza. It was the first com prehensive review on mycologic published researches in Venezuela up to 1959 (169). It represents one of the most pragmatic work carried out by the 'Comisión Coordinadora del Estudio Nacional de la Mycosis' steered and supervised by J. Baldó (169),

(2) Bibliografía Dermatológica Venezolana. This monograph was edited by the Venezuelan protodermatologist Francisco Kerdel-Vegas. It represents the most comprehensive review on dermatology and superficial and deep localized mycoses in Venezuela, which includes papers, monographs, pamphlets, books and chapters in books, updated by 1996 (175).

(3) Micosis Profundas-Datos Generales y Observaciones en Mérida. This manual, edited by K. Salfelder and T. R. Liscano in 1979, is a guide for undergraduate medical students, and eventually for interested specialists. The book covers diagnosis methods, and histopatologic characteristics of cryptococcosis, blastomycosis, paracoccidioidosis, aspergillosis, basidioidomycosis, etc. (176).

(4) Traité de Mycologie Médicale. This is a classical international textbook on medical mycology, where Dante Borelli is a coauthor with J. Delacrétaz and D. Grigouriu. D. Borelli main contribution in this textbook is related with deep localized and systemic mycoses, some therapeutic aspects to treat several mycoses, and techniques to perform laboratory techniques useful to validate clinical and epidemiologic diagnoses on human mycoses (150).

(5) Micología General. This is a textbook written by C. Casas-Rincón. This book covers general aspects of mycology, and specific aspects on human, animal, vegetal mycotic diseases, or practical and industrial applications of fungi. Moreover, it describes environmental fungi contaminants and laboratory techniques to characterize and diagnose fungi (177).

(6) Atlas of Fungal Pathology. This is an amazing colorful manual edited by K. Salfelder, and his collaborators. It is an international highly reputed textbook for surgeons, physicians, dermatologists and pathologists in training. It displays the state of the art knowledge on clinic, histopathology and diagnosis techniques which is supported by 500 illustrations. This book emphasizes the role of opportunistic mycosis syndromes. Authors' main objective was to teach differential diagnoses and morphology of fungi cells (178).

Contribution of Venezuelan General Physicians, Dermatologists and Pathologists to Mycology

Venezuelan pioneer studies on mycoses without pathologic confirmation.

In 1882, D. de Armas published what appears to be the first report on tinea tonsurans treated with salicylic acid and crushed ice (134). Twenty six-years later, in 1908, S. Montiel-Pulgar reported the first case of actinomycetoma (135). Thereafter, many series of cases of several mycoses were published: M.A. Fonseca in 1909 (136), R. Rangel in 1909 (137), Medina-Jiménez (138), R. Pino-Pou in 1917 (139), E. González in 1921 (99), De Bellard in 1924(141), L. Briceño-Iragorry, R. Rísquez in 1929 (179), and P. del Corral in 1934 (143). Details on each author contribution can be seen in Table 6. The above mentioned professionals were general practitioners, medical doctors, medical technologists… One of the Venezuelan protodermatologists, M. Vegas, in 1935, described the first case of sporotrichosis (76). It is worth emphasizing that none of the above reports of cases were confirmed by pathological methods.

Pioneer studies on human mycoses including both dermatologic and pathologic descriptions.

In 1936, R. Jaffé, the pioneer German Venezuelan pathologist, arrived in Venezuela. Jaffé was the master of the new generation of contemporary Venezuelan pathologists. From then on, the join activities of Venezuelan dermatologists and German pathologists, associated or not with medical practitioners, internists, surgeons, otorrhinolaringolo gists… on one hand; laboratory technicians and technologists, on the other hand, published many relevant contributions which consolidate what we dare to call 'the preconstitutional stage of Mycology in Venezuela'.

The relevant pioneer contributions works of dermatologists on human mycoses were initiated by P. Guerra in 1935 (100-102). His trainee, and later technologist, L. de Montemayor (163) and other dermatologists published several papers, say by H. Campíns in 1949-1956 (24, 25, 69-71), D. Borelli in 1957 (64) and Campo de Aasen in 1959 (107).

D. Borelli, through his tenacious work enhanced and internationally put on the spot the mycologic studies in Venezuela. We consider Borelli to be the founder of Mycology as a new scientific discipline in Venezuela. D. Borelli published highly specialized research (64, 80, 147-149), meanwhile he was teaching and training a lot of new professionals on mycology. He is without question the most outstanding Venezuelan mycologist.

Brief review on the German Pathologists' contributions to mycology knowledge, teaching and training in Venezuela.

The following review on relevant data on German pathologists contributions to Mycology in Venezuela were mainly excerpted from the book 'Patólogos Alemanes en Venezuela' (German Pathologists in Venezuela) 1936-1981(180), and from Dr. Salfelder's personal curriculum, other personal communications, and some indexed papers published after 1981. Lets follow this relevant German pathologists 'pathway'. A summary of their main contributions to Venezuela Mycology is displayed on Table 7

No.	Name (ref)	Relevant data on activity developed in Venezuela	Research main contributions	Relevant papers or monographies related to mycoses
1.	Jaffé, R. (1885-1975) (180)	Jaffé arrived in Venezuela in 1936 and started working at the recently found Servicio de Anatomía Patológica (Hospital Vargas) who chairman was J.A. O’Daly, originally founded by J. Rísquez. His main role in Venezuela was to become the ‘maestro’ of many Venezuelan Pathologists including O’ Daly himself.	Despite of the fact that Jafeé did not publish any specific study on mycoses, his teaching and mentor activities were devoted to train many professional who published several papers or mycoses, as mentioned below.	None
2.	Salfelder, K. H. (1919- ) (180)	alfelder arrived in Venezuelan in 1950. Pathologist in Sanatorio Antituberculoso de Oriente (1950-1951). Professor at the University of Los Andes, and chief of the Pathology Service at the Hospital Los Andes and Sanatorio Antituberculoso de Mérida. From 1972 to 1979 was chairman of the Department of Pathology at the Hospital Universitario de Los Andes until his retirement. In 1979 founded the Laboratory of Pathologic Research of the School of Medicine-University of the Andes. Up to 2001 has published more than two-hundred scientific communications, from which 104 are directly or indirectly related to mycoses. We consider Salfelder to be the most relevant pathologist who has published data publishing date on histologic mycological diagnoses in Venezuela.	alfelder’s research on pathology and teaching go beyond the Venezuelan national boundaries. He is an outstanding pathologist worldwide known (alone or collaboration with other multidiscipli-nary co-authors).	Paracoccidioidomycosis: Ecology (16); Review: 19; Chapters in books: 18,20. Histoplasmosis: Clinical and histopathologic descriptions: 28-48; Experimental animal models, 49-59; ecological: 26, 27; Chapters in books: 60-63. Chromomycosis: (Acute) 181-182. Opportunistic mycoses: Aspergillus: 183 Pneumocystis: 184-186. Adiasporomycosis: 187-188. Basidiomycosis: 189, Candida 198, torulosis 199, North America Blastomycosis: experimental: 190; Clinical series: 191; Cryptococcosis: Experimental: 192; histopathology 193; Reviews: 194,195. Sporotrichosis: 196,197. Chromoblastomycosis and others: 200. Several Mycoses: Chromomycosis, cryptococcosis, nocardias: 194; Reviews: 195; Cryptoporidiosis y blastocistosis: 201.
3.	Sauerteig, E. (1919- )	Bolívar founded the Servicio de Anatomía Patológica (Hospital Ruiz y Páez). He was chairman and professor of pathology in the School of Medicine (Universidad de Oriente). Between 1964-1967 worked in Germany (Pathology Institute at Gelsen chirchen). Since 1967 has been chairman of the Department of Pathology, Hospital Luis Razetti, Barinas (Venezuela).	Sauerteig’s mycology studies were on torulosis, histoplasmosis, candidiasis in collaboration with Salfelder. His original contribution is related to rhinosporidiosis in Barinas State, Venezuela.	Rhinosporidiosis: 122. Torulosis: 199. Candidiosis: 193, 198. Histoplasmosis: 34,35. Chromoblastomycosis: 181,182, 200. Cryptococosis: 193. Sporotrichosis: 196,197. Cryptosporidiosis and blastomycosis: 201
4.	Brass, K. (1912- ) (1980)	Brass came to Venezuela in 1950. In Valencia founded and was the chief of the Deparment of Pathology-Hospital Central, and chairman of the Unit of Pathology at the Universidad de Carabobo. Up to 1981 had published 161 scientific contributions, being 13 about mycoses.	Brass’ mycology contributions were on cryptococcosis, deep mycoses, paracoccidioidosis, histoplasmosis, mucomycosis, and aspergillosis.	Cryptococosis: 202. Deep mycoses: 203. Paraccocidioidomycosis 204. Mucormycosis and histoplasmosis: 205. Aspergillosis: 206. Coccidioidomycosis: 207
5.	Doehnert, H. R. (1908-1972) (180)	Doehnert came to Venezuela in 1953; worked as chief of the Department of Pathology at the Hospital Antonio María Pineda; was pathologist of the Sanatorio Antituberculoso of the Hospital del Seguro Social, in Barquisimeto. He founded of the Department of Pathology in the School of Medicine, Universidad Centro Occidental Lisandro Alvarado (UCLA). He published 38 scientific contributions, from which 9 were on mycoses.	Doehnert’s mycologic contributions were on coccidioidomycosis, rhinoporidiosis, pneumocystosis, paracoccidioioidosis, histoplasmosis.	Rhinosporidiosis: 119. Pneumocystosis: 208. Paracoccidioidomycosis: 19, 209, 210. Histoplasmosis: 34-36
6.	Doehnert, G. (1940 )	H.R. Doehnert‘s son became M.D. at the Universidad de Los Andes. He was a Salfelder’s undergraduate student. He worked in the Department of Pathology at Universidad Centro Occidental Lisandro Alvarado and Hospital Antonio María Pineda where his father was the chairman. From 1969 to1973 studied in the Institute of Pathology at the University of Heildelberg (Germany). From 1974-1977 was Professor in Barquisimeto. In 1977 went back to Germany as chief ot the Department of Pathology in the Hospital “San Antonio” in Klevel Niederrhein (Germany).	His contribution to knowledge of mycoses in Venezuela were published in collaboration with Salfelder and HR Doehnert up to 1981. He had published 30 scientific contributions, seven were on mycoses up to 1981.	Pneumocystosis: 208. Paracoccidioidomycosis: 209-210. Histoplasmosis: 34-36
7.	Franz, G. (¿-?) -180	G. Franz arrived in Venezuela in 1952 to work in the Servicio de Anatomia Patológica (Hospital Antituberculoso Maracaibo). He also was pathologist in the Hospital de Niños, Hospital Central, Hospital Psiquiátrico, Hospital Chiquinquirá, Leprocomio (Isla de Toas), and Hospital Coromoto. He also was professor and chairman of the Department of Pathology at the Universidad del Zulia (Maracaibo). Since 1962 he lives in Hamburg (Germany).	From 36 scientific contribution (1954-1962) only two were related to mycoses.	Systemic mycoses: Deep mycoses and Rhizopus 211, 212
8.	Wenger, F. (1913- ) (180)	F. Wenger was pathologist in Bolivia (1939-1945) at the Laboratorio de Histología y Anatomía Patológica , Universidad San Francisco Xavier (Sucre State). He arrived in Maracaibo in 1946, Pathologist of the Laboratorio de Anatomía Patológica (Hospital Central). In 1948 started to work as a pathologist in the Hospital Antituberculoso (Maracaibo) at the Universidad del Zulia. Since 1949 was professor of Pathology at the Universidad del Zulia. Some of his pupils are pathologists.	From 64 scientific contributions published up to 1984, five are related to mycoses.	hinosporidiosis: 213 Paracoccidioidosis: 214 Deep mycoses: 215 Actinomycetoma: 216 Chromoblastomycosis: 217

Table 7

R. Jaffé. Although he did not directly published any contribution on mycoses, he was the master of the most relevant Venezuelan new pathologists trained from the late thirties to the fifties in the twenty Century (180).

K. H. Salfelder. If R. Jaffé was the master of Venezuelan new generation of pathologists in Caracas and Northern Central Venezuela, K. Salfelder has been the mentor and the leader of the new generation of pathologists in Western Venezuela. He is a worldwide recognized scientist not only as pathologist but also as a prominent protozoologist and mycologist. K. H. Salfelder engaged the University of the Andes Medical School in 1951 and retired in 1979. Since then, he established the 'Laboratorio de Investigación en Patología'. This laboratory has been maintained by Salfelder, Teresa Reyes de Liscano and others pathologists, who have co-authored most of the 217 papers and contributions up to 2001, among which 112 papers are related to mycoses. Their papers on mycoses can be summarized as follows: (1) Paracoccidioidomycosis: which includes aspects on ecology (16), experimental studies (17), clinical aspects (18-20). (2) Histoplasmosis: which includes aspects on ecology (20), clinical and histologic aspects (29-48), experimental findings (49-59), chapters in books (60-63). (3) Chromomycosis: which includes case reports of acute infection (181-182), and cases of chromomycosis simultaneously developed with other deep mycoses (200). (4) Opportunistic mycoses: which includes papers on aspergillosis (183); on pneumocystosis (184-186, 199); adiasporomycosis (187, 188). (5) North American blastomycosis: which includes aspects on clinical features (200); experimental (190); reviews (191). (6) Cryptococcosis: which includes papers on experimental (192); on ecology (193), (7) Several mycosis: which includes chromomycosis, cryptococcosis, Nocardia, eumycetoma (181); reviews (195). (8) Sporotrichosis: (196, 197), among others (180).

E. Sauerteig. He was coworker and co-author with Salfelder not only on topics of mycoses, but also in other papers on pathology (180). Sauerteig's papers on rhinosporidiosis may be considered his more original contribution (122). He also wrote cryptococcosis (193), candidiosis (193, 198), histoplasmosis (34, 35), sporotrichosis (196, 197), torulopsis (199), and cryptosporidiosis and blastomicosis (201), and aspergillosis (206).

K. Brass. His research, carried out in Valencia (Central Venezuela), was mainly addressed to Chagas' disease (180). His contributions on mycoses were related to cryptococcosis (202), deep mycoses (203), paracoccidioidomycosis (204), histoplasmosis (205), and aspergillosis (206).

H. R. Doehnert. German pathologist who worked in Barquisimeto (Central-Western Venezuela) (180). His contribution to mycology were on coccidioidomycosis (207), pneumocystosis (208), paracoccidioidomycosis (19, 209, 210), histoplasmosis (34-36), and rhinosporidiosis (119).

G. Doehnert. Son of H. R. Doehnert, graduated at the Universidad de Los Andes (Mérida, Venezuela) and trained in pathology by Dr. K. Salfelder (180). He was co-author of papers on histoplasmosis (34-36), paracoccidioidomycosis (209), several infections (209).

G. Franz. He published a paper on pathologic finding on human systemic mycoses (162). and other on rhyzopus (212).

F. Wenger. German pathologist who, after residing in Ecuador, worked in Maracaibo (Universidad del Zulia) (180) with respect to mycology, he published a paper on rhinosporidiosis (213). Other, on lymphatic paracoccid ioidomycosis (214), deep mycoses (215), actinomycetoma (216), and chromomycosis (217).

Final Remark

Table 7 epitomizes the special contributions of German pathologists to built-up the 'constitutional stage' of mycology studies in Venezuela. The main achievement of German pathologists in Venezuela was to introduce histopathologic characterization, laboratory techniques and demonstration of mycotic agents in patients which final diagnoses were unknown then and there. Their contributions allowed completing final diagnoses of clinical organic pathologies, and to make differential pathological diagnoses among fungi themselves, fungi and bacteria, and fungi and protozoa.

The section 'Development of teaching diagnostic laboratory mycoses Techniques through institutional working groups in Venezuela' described most relevant data on the history of Venezuelan mycologists up to 1998.

In 1981, K. Salfelder and D. Novoa-Montero edited a monograph entitled "Patólogos Alemanes en Venezuela. 1936-1981". (German pathologist in Venezuela. 1936-1981) (180), which is the main source of data for this section of the paper.

Ultimately, Mycology in Venezuela has received the contributions of chemists and biologists G. de San-Blas and F. San-Blas (21, 22); ultrastructural aspects (J. A. Serrano (96), Serrano also published a biomedical-social aspects of eumycetoma (218); biological and mycological aspects (Yegres and Richard-Yegres, 90-93); and serological and immunological studies (H. Romero, 155-157), among other outstanding researchers, some of them included in previous comments (Table 6).

A recent review on historical aspects on the development of the Mycology in Venezuela was published by Briceño-Maaz et al as a 'Breve historia de la micología médica en Venezuela' (219). Finally, on amazing review was wrote down by G. de San Blas, 'A journey through Latin American Medical mycology', where the Venezuelan historical development and relevant papers on mycologic aspects up to 2000 are included (22).

Acknowledgements

We acknowledge Dr. P. Venugopal (India) her critical comments to improve editing of this paper. This manuscript was carefully typed several times by Ana Uzcátegui de Camargo, Secretary of Lab-MICE.

German-Venezuelan Pathologists-Mycologists.
Rudolf Jafee (1885-1975).	Karl Brass (1912).	Hans R. Doehnert (1908-1972).	Karlhans Salfelder (1919).
Early and middle XX Century Venezuelan Mycologists.
Pablo Guerra (1903-1944).	Enrique Tejera (1909-1980).	José A. O’Daly (1908).	Lorenzo de Montemayor
Middle and late XX Century Venezuelan Mycologists.
Tulio Briceño Maaz (1907).	Humberto Campíns (1911-1998).	José Hómez Chacín (1921).	Dante Borelli (1920-1997 ).
Late XX Century and new Millennium Venezuelan Mycologists.
Felipe San Blas	Gioconda Cunto de San Blas	Nicolle Richard de Yegres (1939).	José Francisco Yegres (1941).
Late Century and new Millennium Venezuelan Mycologists.
María C. Bastardo de Albornoz	María A. Mejía de Alejo (1937)	José Antonio Serrano R. (1938).	Darío Novoa-Montero (1937).

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13. Baldó, J.: Paracoccidioidomicosis pulmonar. Revista Sanidad Asistencia Social;163-176, 1953.        [ Links ]

14. Moncada, F.; Salfelder, K. y Hartung, M.: Comentarios de un caso de blastomicosis suramericana. Revista Colegio Médicos, Edo. Mérida; 7: 369-374, 1957.        [ Links ]

15. Avendaño-Monzón, R.: Paracoccidioidomicosis. Casuística en el Sanatorio "Venezuela" Mérida. Universidad de Los Andes, Facultad de Medicina, Talleres Gráficos Universitarios, 1970.        [ Links ]

16. Mendolovici, M. de; Salfelder, K.; Mendelovici, E. y Román, A. de: Intento de aislamiento del Paracoccidioides brasiliensis del suelo. Mycopath. and Mycol. Appl.; 52:45-53, 1974.        [ Links ]

17. Salfelder, K.; Schwarz, J.: Experimental cutaneous South American blastomycosis in hamsters. Arch. Derm.; 77:68-77, 1968.        [ Links ]

18. Salfelder, K.; Hartung, M.: Paracoccidioidomycosis. Clinical Dermatology: A Source Book of Skin Diseases. Harper and Row. New York. Vol. 3: Sect.; 17-21,1-13. 1972.        [ Links ]

19. Salfelder, K.; Doehnert, G. and Doehnert, H. R.: Paracoccidioidomycosis. Virchows. Arch. Abt. A. Path. Anat.; 348:51-76, 1969.        [ Links ]

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24. Campíns, H. y Shary, M.: Comprobación de las histoplasmosis en Venezuela. Gaceta Médica de Caracas; 61:67-75, 1953.        [ Links ]

25. Campíns, H.; Zubillaga, Z.; Gómez-López, L. and Dorante, M.: An epidemic of histoplasmosis in Venezuela. Am J Trop Med & Hyg.; 5:690-695, 1956.        [ Links ]

26. Capretti, C.; Salfelder, K. y Romero, A.: Histoplasma capsulatum en el suelo de nuestro ambiente. Exámenes micológicos. Mycopath. et Mycol.; 17:55-70, 1963.        [ Links ]

27. Salfelder, K.: Búsqueda de Histoplasma capsulatum en una cueva de La Azulita, Estado. Mérida,. Ediciones de la Corporación de Los Andes, Mérida, Venezuela, 1966.         [ Links ]

28. Salfelder K. Zur Differential diagnose der Histoplasmose. Z. Tropenmed. Parasit.; 11: 453-469, 1960.        [ Links ]

29. Salfelder, K. y Capretti, C.: Primoinfección pulmonar de histoplasmosis en un lactante. Mycopath. 1961; 15:251-257, 1961.        [ Links ]

30. Hartung, M. und Salfelder, K.: Histoplasmose mit toedlichem Ausgang als Derufserkrankung bei einem Mykologen. Arch. Gewerbepath.; 19:270-289, 1962.        [ Links ]

31. Salfelder, K.; Romanovich, J.; Liscano, T. R. de und Moncada, F.: Ueber einen fall von Lungenhistoplasmom mi moeglicher infection in italien. Mykosen.; 6:29-34, 1963.        [ Links ]

32. Salfelder, K.: Fatal case of erythema nodosum and histoplasmosis. Mycopath., 22:315-321, 1964.        [ Links ]

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35. Salfelder, K.; Doehnert, G.; Doehnert, H. R.; Brass, K. und Sauerteig, E.: Histoplasmose. Zahl der lungenherde bei der Primaerinfektion. Dtsch. Med. Wschr.; 95:2125-2128, 1970.        [ Links ]

36. Salfelder, K.; Brass, K.; Doehnert, G. und Doehnert, H. R.: Histoplasmose, Gewebliche Struktur U. Entwicklung primarer Lungenherde. Mykosen; 14: 159-167, 1971.        [ Links ]

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39. Schwarz, J.; Salfelder, K. and Viloria, J. E.: Histoplasma capsulatum in Vesseks of the Chroroid. Ann Ophth.; 9:633-636, 1977.        [ Links ]

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42. Salfelder, K.; Sauerteig, E.; Liscano, T. R de; Hernández, P. R. y García, M.: Selten zu Sehen: Histologische und Zgtologische Befunde bei der Histoplasmose-Teil I. Hautnah Derm.; 5:322, 1996.        [ Links ]

43. Salfelder, K.; Sauerteig, E.; Liscano, T. R. de; Hernández, P. R. und García, R. M.: Histologische und Zytologische Befunde bei der Histoplasmose-Teil II. Hautnah Derrn.; 6: 398, 1997.        [ Links ]

44. Salfelder, K.; Liscano, T. R. de: Sauerteig, E.; García, R. M.; Borregales, E.; Pérez, S. N.; Sepúlveda, S. und Hernández, P. R.: Klinische diagnose der Histoplasmose mittlles Histologie und Zytologie-Teil 2. Derm.; 3: 24, 1997.        [ Links ]

45. Salfelder, K.; Liscano, T. R de; Sauer teig, E.; García, R. M.; Borregales, E.; Pérez, S. N.; Sepúlveda, S. und Hernández, P. R.: Klinische Diagnose der Histoplasmose mittels Histologie und Zytologie-Teil 2derrn.; 3:118, 1997.        [ Links ]

46. Salfelder, K. y Liscano, T. R. de.: Lesiones histoplasmóticas autópsicas como índice epidemiológico de la enfermedad en Los Andes venezolanos. Mycopath.; 26: 19-30, 1965.        [ Links ]

47. Salfelder, K. und Schwarz, J.: Histoplasmotische Klalherde in der Milz. Dtsch Med Wschr.; 92:1450-1470, 1967.        [ Links ]

48. Salfelder, K.; Liscano, T. R. de y Hartung, M.: Estudios sobre Histoplasmosis. Revista Colegio de Médicos. Mérida (Ven); 28/29:23-35, 1969.         [ Links ]

49. Salfelder, K. and Schwarz, J.: Histoplasma capsulatum in chickens. Mykosen.; 10: 337-3650, 1967.        [ Links ]

50. Salfelder, K. and Schwarz, J.: Cross reactions to Histoplasma capsulatum in mice. Sabouraudia, 3:164-166, 1964.        [ Links ]

51. Akbarian, M.; Salfelder, K. and Schwarz.: Experimental histoplasmosis endocarditis. Arch. Int. Med., 114: 784-791, 1964.        [ Links ]

52. Salfelder, K.; Capretti, C. and Romero, A.: Histoplasma capsulatum im Boden II. Morphologischer Pilznachweis, Gewebsreaktionen und Vergleich der Kulturversuche mit den histologischen Untersuchungen bei Mauesen. Mycopath.; 19:62-82, 1963.        [ Links ]

53. Salfelder, K. and Schwarz, J.: Experimental cutaneous histoplasmosis in hamsters. Arch. Derm.; 91:645-656, 1965.        [ Links ]

54. Salfelder, K.; Sethi, K. K. and Schwarz J. Experimental histoplasmosis in temporarily hibernating hamsters. Mycopath.; 27:289-300, 1965.         [ Links ]

55. Salfelder, K. y Schwarz, J.: Adiasporomicosis experimental en ratas y hamsters. Revista Colegio de Médicos. Estado. Mérida (Ven); 34:12-19, 1975.        [ Links ]

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