Proceedings of the second international meeting on endemic mycoses of the Americas (IMEMA) and first international symposium on implantation mycoses (ISIM).

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

[Tinea capitis: clinical features and therapeutic alternatives]. / Tinea capitis: aspectos clínicos y alternativas terapéuticas.

A descriptive observational and cross-sectional study was carried out. The clinical characteristics, etiologic agents, treatments and outcome of 33 cases of tinea capitis in the Mycology Unit at Francisco J. Muñiz Hospital of Buenos Aires City between January 2015 and December 2019 were analyzed. The median age of the patients was 7 years, 21 of whom were male, 3 were HIV-positive and 22 had pets. The isolated etiologic agents were the following: Microsporum canis in 22 cases, Trichophyton tonsurans in 8, Nannizzia gypsea in 2 and Trichophyton mentagrophytes in one patient. Suppurative tinea capitis (krion Celsi) was detected in 10 cases and the same number of patients presented other skin locations of their dermatophytosis in addition to those in the scalp. Twenty-one cases were orally treated with griseofulvin and 12 with terbinafine. Those patients with suppurative tinea capitis received drops of betamethasone by mouth besides the antifungal drugs. All patients had good clinical and mycological response to the treatments, all lesions disappeared, and mycological studies turned negative by the end of the treatments. We conclude that both drugs were effective for the treatment of tinea capitis; however, lesions in those cases receiving terbinafine involuted more slowly.

Inherited CARD9 Deficiency in a Patient with Both Exophiala spinifera and Aspergillus nomius Severe Infections.

PURPOSE: Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary Aspergillus infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency. MATERIALS AND METHODS: Genetic analysis was performed by Sanger sequencing. Neutrophils and mononuclear phagocyte response to fungal stimulation were evaluated through luminol-enhanced chemiluminescence and whole blood production of the proinflammatory mediator interleukin (IL)-6, respectively. RESULTS: We report a 56-year-old Argentinean woman, whose invasive Exophiala spinifera infection at the age of 32 years was unexplained and reported in year 2004. At the age of 49 years, she presented with chronic pulmonary disease due to Aspergillus nomius. After partial improvement following treatment with caspofungin and posaconazole, right pulmonary bilobectomy was performed. Despite administration of multiple courses of antifungals, sustained clinical remission could not be achieved. We recently found that the patient's blood showed an impaired production of IL-6 when stimulated with zymosan. We also found that she is homozygous for a previously reported CARD9 loss-of-function mutation (Q289*). CONCLUSIONS: This is the first report of a patient with inherited CARD9 deficiency and chronic invasive pulmonary aspergillosis (IPA) due to A. nomius. Inherited CARD9 deficiency should be considered in otherwise healthy children and adults with one or more invasive fungal diseases.

Genomic diversity of the human pathogen Paracoccidioides across the South American continent.

Paracoccidioidomycosis (PCM) is a life-threatening systemic mycosis widely reported in the Gran Chaco ecosystem. The disease is caused by different species from the genus Paracoccidioides, which are all endemic to South and Central America. Here, we sequenced and analyzed 31 isolates of Paracoccidioides across South America, with particular focus on isolates from Argentina and Paraguay. The de novo sequenced isolates were compared with publicly available genomes. Phylogenetics and population genomics revealed that PCM in Argentina and Paraguay is caused by three distinct Paracoccidioides genotypes, P. brasiliensis (S1a and S1b) and P. restrepiensis (PS3). P. brasiliensis S1a isolates from Argentina are frequently associated with chronic forms of the disease. Our results suggest the existence of extensive molecular polymorphism among Paracoccidioides species, and provide a framework to begin to dissect the connection between genotypic differences in the pathogen and the clinical outcomes of the disease.

[Cryptococcal meningitis in patients with diabetes and AIDS]. / Criptococosis meníngea en pacientes con diabetes y sida.

INTRODUCTION: Cryptococcal meningitis is a severe AIDS-related infectious disease, with a high mortality rate. Diabetes mellitus (DM) is a metabolic disorder very common worldwide. Infectious diseases in diabetic patients are always more severe than in non-diabetic ones. The aim of this study was to compare the outcome of a group of HIV-positive patients with DM and cryptococcal meningitis with a similar group HIV-positive patients with cryptococcal meningitis, but without DM. MATERIAL AND METHODS: A total of 182 clinical records of HIV-positive patients suffering cryptococcal meningitis were reviewed, and 28 of them with similar clinical and epidemiological characteristics, were chosen. They included 14 patients with DM (group A) and the remaining 14 who did not suffer this metabolic disorder (group B). RESULTS: Only 21.4% (3/14 cases) of group A patients had negative CSF cultures after 10 weeks of treatment. In group B patients, 78.5% (11/14 cases) achieved negative CSF cultures before 10 weeks. A higher overall mortality rate was observed in the diabetic patients (85.7%, 12/14 cases) than in the non-diabetic group (21.4%, 3/14 cases). All CSF isolates were identified as Cryptococcus neoformans, and all strains were susceptible in vitro to amphotericin B and fluconazole. CONCLUSIONS: Cryptococcal meningitis in diabetic patients was associated with a poor clinical outcome and a high mortality rate. A longer treatment induction period is suggested in order to improve the outcome of cryptococcal meningitis in diabetic patients.

[Clinical problems in Medical Mycology: Problem number 56]. / Problemas clínicos en Micología Médica: problema número 56.

We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up.

Evaluation of an enzyme immunoassay technique on detecting urinary Histoplasma capsulatum antigen in the diagnosis of disseminated histoplasmosis in Argentina.

INTRODUCTION: Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. METHODS: In this retrospective, longitudinal and analytical study, carried out over a period of 2 years, the sensitivity (S) and specificity (E) of a commercial kit for the detection of Histoplasma antigen by EIA technique (HC-Ag) was evaluated in 50 patients with AIDSassociated histoplasmosis. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. RESULTS: HC-Ag had a S of 94%, E 96%, positive likelihood coefficient (CVP): 20.68 and negative likelihood coefficient (CVN): 0.06. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S to 100%; with similar values in E. CONCLUSION: The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Introducción: La histoplasmosis es una micosis sistémica de distribución universal, altamente endémica en las Américas. Es causada por un hongo dimórfico: Histoplasma capsulatum var. capsulatum. Afecta tanto a inmunocompetentes como a inmunocomprometidos, se observan formas progresivas y diseminadas. Un factor de riesgo muy importante es la infección por HIV/sida, con una tasa de mortalidad del 20-40% en América Latina. El diagnóstico de esta micosis se realiza por métodos convencionales y moleculares o por detección de antígenos y anticuerpos. Métodos: En este estudio retrospectivo, longitudinal y analítico, realizado en un periodo de 2 años, se evaluó la sensibilidad (S) y especificidad (E) de un kit comercial para la detección de antígeno de Histoplasma por técnica de EIA (HC-Ag) en 50 pacientes con histoplasmosis asociada a sida. Además, se comparó su rendimiento con el de otras técnicas diagnósticas utilizadas habitualmente en nuestro laboratorio. Resultados: HC-Ag tuvo una S del 94%, E del 96%, coeficiente de verosimilitud positiva (CVP) de 20.68 y coeficiente de verosimilitud negativa (CVN) de 0.06. El tiempo de demora de los resultados fue de 4 días, similar al de la detección de anticuerpos y n-PCR y mucho menor que el de los hemocultivos. La combinación de métodos mejoró la S a 100%; con valores similares en E. Conclusión: El método HC-Ag demostró su utilidad en el diagnóstico de histoplasmosis diseminada progresiva y la combinación de métodos es una buena opción para aumentar la sensibilidad y disminuir el tiempo para llegar al diagnóstico de certeza. Esto permite mejorar la estrategia en el manejo de la enfermedad y reducir su tasa de letalidad.

High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species.

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140-143,912 SSR loci were identified (82,841-98,369 unique markers), with a 3651.55-3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.

Standardization and characterization of antigens for the diagnosis of aspergillosis.

The aim of this study was to develop and characterize antigens for the diagnosis of aspergillosis. Nine strains of Aspergillus species Aspergillus fumigatus , Aspergillus flavus , and Aspergillus niger were grown in Sabouraud and Smith broth to produce exoantigens. The antigens were tested by immunodiffusion against sera from patients with aspergillosis and other systemic mycoses. The protein fraction of the antigens was detected by SDS-PAGE; Western blot and representative bands were assessed by mass spectrometry coupled to a nano Acquity UltraPerformance LC and analyzed by the Mascot search engine. Concurrently, all sera were tested with Platelia Aspergillus EIA. The most reactive antigens to sera from patients infected by A. fumigatus were produced by A. fumigatus MG2 Sabouraud and pooled A. fumigatus Sabouraud samples, both with a sensitivity of 93% and specificity of 100% and 97%, respectively. Aspergillus niger and A. flavus antigens were reactive against A. niger and A. flavus sera, each one with a sensitivity and specificity of 100%. Two proteins, probably responsible for antigenic activity, ß-glucosidase in A. fumigatus and α-amylase in A. niger were attained. The commercial kit had a specificity of 22%, sensitivity of 100%, positive predictive value of 48%, and negative predictive value of 100%. The antigens produced showed high sensitivity and specificity and can be exploited for diagnostics of aspergilloma.

[Disseminated infection due to Penicillium marneffei related to HIV infection: first observation in Argentina]. / Infección diseminada por Penicillium marneffei en un paciente HIV-positivo: Primera observación en la República Argentina.

The first case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identification was confirmed by rRNA amplification and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

Chronic recurrent vulvovaginitis is not only due to Candida.

BACKGROUND: Recurrent vulvovaginitis is a growing problem that affects millions of women worldwide. In many cases it is treated as vulvovaginal candidiasis, but there is not always microbiological confirmation. AIMS: To determine the etiology of vulvovaginitis in a group of patients. METHODS: This is a cross-sectional study in which the data from the medical records of 316 adult patients who consulted for vulvovaginitis were analyzed. Eighty nine percent of the cases had already suffered previous episodes. RESULTS: The median age was 34 (265 patients were between 16 and 45 years old). Yeasts were isolated in culture from 211 (66.8%) patients, although pseudo-hyphae and yeasts were observed in only 166 samples (52.5%) in the direct microscopic examination. Multiple predisposing factors were found, among which the use of contraceptives or previous antibiotics stand out. Most of the patients (almost 90%) had been treated with antifungals, with or without microbiological confirmation. Candida albicans was isolated in 187 (88.6%) patients, followed by Candida glabrata in 6 (2.8%) patients. Association with bacterial vaginosis was found in 35.1% and with intermediate bacterial microbiota in 33.2% of the cases. A remarkably high proportion of C. albicans isolates resistant to fluconazole (80.1%) and itraconazole (58.8%) was found. CONCLUSIONS: A microbiological analysis is essential to confirm the diagnosis of vulvovaginal candidiasis, whether simple, complicated, or recurrent. Identifying the isolated yeast species and determining its susceptibility to antifungal agents are particularly important.

Tongue lesion due to Cryptococcus neoformans as the first finding in an HIV-positive patient.

BACKGROUND: Cryptococcosis is a severe universally distributed mycosis which mainly affects immunocompromised hosts. This mycosis is caused by yeasts of two species complex of the genus Cryptococcus: Cryptococcus neoformans and Cryptococcus gattii. Meningeal cryptococcosis is the most frequent clinical presentation of this disseminated mycosis. The oral mucosa involvement is extremely unusual. CASE REPORT: We present a case of cryptococcosis with an unusual clinical form. The patient was assisted because she had an ulcerated lesion on the lingual mucosa. Encapsulated yeasts compatible with Cryptococcus were found in microscopic exams of wet preparations from lingual ulcer clinical samples obtained for cytodiagnosis and mycological studies. Cryptococcus neoformans (C. neoformans var. grubii VNI) was isolated in culture. This patient did not know her condition of HIV seropositive before the appearance of the tongue lesion. CONCLUSIONS: The involvement of the oral mucosa is uncommon in this fungal infection, but is important to include it in the differential diagnosis in HIV positive patients.

A new duplex PCR assay for the rapid screening of mating-type idiomorphs of pathogenic Sporothrix species.

Sporothrix schenckii and allied species are thermodimorphic fungi widely distributed in nature which causes human and animal sporotrichosis, the most common subcutaneous mycosis globally. Sporotrichosis is acquired after a traumatic inoculation of soil or plant material contaminated with Sporothrix propagules or through bites and scratches from diseased cats. In Ascomycota, the master regulators of sex are MAT genes that lie in a single mating-type locus, in Sporothrix these are determined by two nonhomologous alleles, MAT1-1 and MAT1-2. We assessed the whole-genome sequences of medically relevant Sporothrix to develop a single-tube duplex PCR assay to screen S. brasiliensis, S. schenckii, S. globosa, and S. luriei idiomorphs (MAT1-1 or MAT1-2) and understand the distribution and incidence of mating-type strains from natural populations. Using our duplex PCR assay, a 673 bp amplicon (α-box protein) was consistently amplified from all MAT1-1 isolates, while a 291 bp fragment was only amplified from the isolates harboring MAT1-2 (HMG box). Molecular evidence suggests heterothallism (self-sterility) as the unique mating strategy among the species evaluated. The mating-type identity of 93 isolates revealed a nearly equal distribution (1:1 ratio) of mating type alleles within species but deviating between different outbreak areas. Remarkably, for S. brasiliensis in Rio de Janeiro, we report an overwhelming occurrence of MAT1-2 (1:13 ratio; χ2 = 10.286, P = 0.0013) opposing the high prevalence MAT1-1 in the Rio Grande do Sul (10:1 ratio; χ2 = 7.364, P = 0.0067). Therefore, the population structure of Sporothrix species refers from paucity to regular cycles of sexual recombination in most of the studied regions. Our PCR-based mating-type diagnostic assay is proposed here as an important marker to track the geographical expansion during the long-lasting outbreak of cat-transmitted sporotrichosis driven by S. brasiliensis.

Fungal cerebral abscess in a diabetic patient successfully treated with surgery followed by prolonged antifungal therapy.

BACKGROUND: Intracranial fungal masses are uncommon diseases, but their incidence is increasing, most often due to the prolonged survival of patients with different immunodeficiencies. The management of patients with intracranial fungal masses included stereotactic biopsy for diagnosis, partial or radical surgery excision and prolonged antifungal therapy. AIMS: We report the case of a 51-year-old diabetic man with a history of psoas abscess due to Candida albicans 1 year before the onset of neurological symptoms, including headache and generalized tonoclonic seizures. METHODS: Magnetic resonance imaging showed a single lesion located in the right parietal lobe with mass effect, surrounding edema and enhancement after injection of gadolinium. The material was purulent. RESULTS: Direct microscopic examination showed hyaline, branched and septate hyphae compatible with fungal elements. CONCLUSIONS: Fungal infections, especially due to Candida species, should be considered in diabetic patients with parenchymal brain abscesses. Radical excision followed by prolonged antifungal therapy based on fluconazole or amphotericin B is necessary to improve the prognosis of this type of patients.

Renal abscess due to Aspergillus fumigatus as the only sign of disseminated aspergillosis in a patient with AIDS.

BACKGROUND: Aspergillus fumigatus can cause a wide variety of clinical syndromes, especially in the three largest immunocompromised groups, such as HIV-infected patients. Primary renal aspergillosis is an extremely rare entity. AIMS: We report an unusual case of renal abscess due to Aspergillus fumigatus in a patient with AIDS. METHODS: We review clinical and laboratory records, and provide follow up of the patient. RESULTS: A 38-year-old man, HIV seropositive, was admitted to our hospital with fever, lumbar pain and respiratory symptoms. Abdominal ultrasound and computerised tomography showed a single and large lesion consistent with an abscess located in the left kidney. Aspergillus fumigatus was isolated from clinical sample obtained by ultrasound-guided needle aspiration. Despite a correct treatment based on amphotericin B and drainage of the abscess, surgery was necessary and nephrectomy was carried out. Histopathological examination of the surgical specimen confirmed the diagnosis of renal aspergillosis. Systemic antifungal therapy based on intravenous and oral voriconazole and highly active antiretroviral therapy was started after surgery. The patient had a good response to the established treatment and he remains in a good clinical condition at one year of follow up. CONCLUSIONS: Combined medical and surgical treatment is the elective therapy for renal abscesses due to Aspergillus when percutaneous drainage and the administration of systemic antifungal drugs, such as amphotericin B and/or oral voriconazole or itraconazole, fail. This case emphasizes renal fungal infections should be included in the differential diagnosis of kidney abscesses in AIDS patients.

[Clinical problems in medical mycology: problem number 53]. / Problemas clínicos en micología médica: problema número 53.

A 21 year-old man, HIV infected, and with poor adherence to antiretroviral treatment, consulted us due to a papular rash on trunk and extremities, showing simultaneously hypochromic stains on his back. He was afebrile and hemodynamically stable. In the mycological study of the clinical samples taken from different lesions, yeasts compatible with Malassezia were observed. Oral itraconazole was prescribed, with an excellent clinical response. Finding the same etiolologic agent in 2different clinical pictures on a single patient is extremely rare.

Antifungal Resistance in Clinical Isolates of Aspergillus spp.: When Local Epidemiology Breaks the Norm.

Aspergillosis is a set of very frequent and widely distributed opportunistic diseases. Azoles are the first choice for most clinical forms. However, the distribution of azole-resistant strains is not well known around the world, especially in developing countries. The aim of our study was to determine the proportion of non-wild type strains among the clinical isolates of Aspergillus spp. To this end, the minimum inhibitory concentration of three azoles and amphotericin B (used occasionally in severe forms) was studied by broth microdilution. Unexpectedly, it was found that 8.1% of the isolates studied have a diminished susceptibility to itraconazole. This value turned out to be similar to the highest azole resistance rate reported in different countries across the world.

[Cavitary pneumonia in an AIDS patient with cryptococcosis]. / Neumonía cavitada por Cryptococcus neoformans en un paciente con sida.

Pulmonary cryptococcosis is an unusual fungal infection that is most often found in AIDS or in organ transplant recipients. Although in immunocompromised patients, cryptococcal infection often causes pulmonary infections, the diagnosis of lung involvement is generally difficult. The presentation of pulmonary cryptoccosis in HIV-infected patients appears to be more acute and severe than in other immunocompromised patients, probably related with the severe immunosuppression. Diffuse infiltrates, mediastinal and hilar lymph nodes enlargement are the most common radiological findings in AIDS-associated pulmonary cryptococcosis. Cavitation is a rare form of and includes only 10% to 15% of all cases. Only a few case reports or studies with small number of patients of pulmonary cryptococcosis have been published over the past two decades. We report a case of an AIDS patient who developed cavitary pneumonia as the only clinical expression of cryptococcosis.

Magnetic resonance imaging findings in AIDS patients with central nervous system cryptococcosis.

Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus neoformans. Generally, the disease affects the central nervous system, especially in patients with human immunodeficiency virus infection. Central nervous system involvement can be either meningeal or parenchymal. As the infection spreads along the Virchow-Robin spaces these structures may dilate with the mucoid and gelatinous material produced by the organism's capsule. The lesions associated with the dilatation of Virchow-Robin spaces are referred to as gelatinous pseudocysts. Bigger lesions are known as cryptococcomas. In this article we describe five patients with neurocryptococcosis associated with AIDS and parenchymal lesions compatible with gelatinous pseudocysts and cryptococcomas.

Disseminated nocardiosis with psoas abscess in a patient with AIDS: first reported case.

Psoas muscle abscess is an uncommon infection that have been diagnosed increasingly in the last years. We present a case of a patient with advanced human immunodeficiency virus infection who developed a disseminated infection due to Nocardia asteroides sensu stricto type VI with psoas abscess. To our knowledge no other cases of Nocardia psoas abscess in the setting of HIV infection have been reported in the literature.