Histoplasmin Skin Test Research Articles

Screening for acute disseminated histoplasmosis in HIV disease using urinary antigen detection enzyme immunoassay: A pilot study in Cameroon

Acute disseminated histoplasmosis (ADH) is an AIDS-defining illness and reported in Cameroon, but there are few data about its incidence. Between June and August 2019, we conducted a descriptive cross-sectional study to screen for histoplasmosis in a population of adults with HIV infection, irrespective of their CD4 T-cell counts, using Histoplasma urine antigen detection enzyme immunoassay (EIA) and histoplasmin skin test. Of the 138 participants screened, 36 (26%) had detectable antigen in urine, using an OD cut off of 0.045. Skin lesions were present in two (6%) cases. Of 39 patients tested for histoplasmin skin test positivity, one was positive. Histoplasma antigenuria was associated with a positive history of chest infection (Odds ratio: 3.632, 95% confidence interval: 1.635–8.071, p= 0.001). As 30 (21.7%) of titres were between 0.045 (the current cut off) and 0.25, the cut off may need adjustment in Cameroon, using disease confirmation with alternative, highly sensitive diagnostic approaches such as PCR and bone marrow examination. H. capsulatum infection appears to be common among HIV-infected patients attending outpatient clinics at the Buea Regional Hospital. There is an acute need to improve awareness and management of HIV patients with respect to H. capsulatum infection.

Mapping histoplasmosis in South East Asia – implications for diagnosis in AIDS

ABSTRACT Histoplasmosis caused by the fungus Histoplasma capsulatum is often lethal in patients with AIDS. Urine antigen testing is highly sensitive and much quicker for diagnosis than culture. Histoplasmosis has a patchy and incompletely appreciated distribution around the world especially in South East Asia. We conducted a systematic literature review of cases of all disease forms of histoplasmosis in SE Asia, not including the Indian sub-continent. We also reviewed all histoplasmin skin test mapping studies to determine localities of exposure. We found a total of 407 cases contracted or likely to have been contracted in SE Asia. Numbers of cases by country varied: Thailand (233), Malaysia (76), Indonesia (48) and Singapore (21), with few or no cases reported in other countries. Most cases (255 (63%)) were disseminated histoplasmosis and 177 (43%) cases were HIV associated. Areas of high histoplasmin skin test sensitivity prevalence were found in Myanmar, the Philippines, Indonesia, Thailand and Vietnam - 86.4%, 26.0%, 63.6%, 36.0% and 33.7%, respectively. We have drawn maps of these data. Further study is required to ascertain the extent of histoplasmosis within SE Asia. Diagnostic capability for patients with HIV infection is urgently required in SE Asia, to reduce mortality and mis-diagnosis as tuberculosis.

Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study

Fungal infections remain a major contributor to the opportunistic infections that affect people living with HIV. Among them, histoplasmosis is considered neglected, often being misdiagnosed as tuberculosis, and is responsible for numerous deaths in Latin America. The objective of this study was to estimate the burden of HIV-associated histoplasmosis compared with tuberculosis in Latin American countries. For this modelling study, we estimated prevalence of previous exposure to Histoplasma capsulatum, HIV-associated histoplasmosis annual incidence, and number of deaths in 2012 in Latin American countries based on historical histoplasmin skin test studies in the general population, with an antigen dilution level of more than 1/10. Studies were identified in a literature search. Data on HIV-associated tuberculosis were extracted from the WHO notifications and outcomes tables and data on people living with HIV were extracted from the UNAIDS report for the year 2012. We systematically propagated uncertainty throughout all the steps of the estimation process. Among 1310 articles identified as of June 1, 2015, 24 articles were included in the study, representing 129 histoplasmin skin test studies led in the general population of Latin American countries. For the year 2012, we estimated a range of 6710 (95% CI 5680-7867) to 15 657 (13 254-18 357) cases of symptomatic HIV-associated histoplasmosis in Latin America. Hotspot areas for histoplasmosis prevalence (>30%) and incidence (>1·5 cases per 100 people living with HIV) were Central America, the northernmost part of South America, and Argentina. According to realistic scenarios, we estimated a range of 671 (95% CI 568-787) to 9394 (7952-11 014) deaths related to histoplasmosis, compared with 5062 (3777-6405) deaths related to tuberculosis reported in Latin America. Our estimates of histoplasmosis incidence and deaths are high and consistent with published data. For the first time, the burden of histoplasmosis is estimated to be equivalent in incidence and even higher in deaths when compared with tuberculosis among people living with HIV in Latin America. None.

Prior subclinical histoplasmosis revealed in Nigeria using histoplasmin skin testing.

ObjectivesDisseminated histoplasmosis is an AIDS-defining illness. Histoplasmosis is commonly misdiagnosed as tuberculosis. Nigeria has the second highest number of people living with HIV/AIDS in Africa. The present study was carried out to investigate the prevalence of skin sensitivity amongst Nigerians to histoplasmin.DesignA cross-sectional study was conducted in six centres across five geopolitical zones of Nigeria.MethodsWe recruited both healthy non-HIV and HIV-positive adults with CD4 count ≥ 350 cells/mm3 regardless of their ART status from March to May 2017. Skin tests were performed intradermally; induration ≥5 mm were considered to be histoplasmin positive.Results750 participants were recruited from Lagos (n = 52), Yola (n = 156), Ilorin (n = 125), Calabar (n = 120), Ibadan (n = 202) and Benin (n = 95). 467 (62.3%) were HIV negative, 247 (32.9%) were HIV positive and 36 (4.8%) did not know their HIV status. A total of 32/735 (4.4%) participants had a positive skin test. Study centre (p<0.001), education (p = 0.002) and age (p = 0.005) appeared to be significantly associated with positive skin reactivity at the 0.5% significance level, while sex (p = 0.031) and occupation (p = 0.031) would have been significant at the 5% significance level. Males had a higher rate of reactivity than females (p = 0.031, 7% vs 3%). The highest positive rates were recorded from Benin City (13/86 (15%)) and Calabar (7/120 (6%)) and no positives were recorded in Lagos (p<0.001). HIV status was not statistically significant (p = 0.70).ConclusionHistoplasmosis diagnostics should be included in the Nigerian HIV guidelines. Epidemiological vigilance of progressive disseminated histoplasmosis should be considered by local health authorities.

Histoplasmosis in Africa: An emerging or a neglected disease?

Histoplasmosis in Africa has markedly increased since the advent of the HIV/AIDS epidemic but is under-recognised. Pulmonary histoplasmosis may be misdiagnosed as tuberculosis (TB). In the last six decades (1952–2017), 470 cases of histoplasmosis have been reported. HIV-infected patients accounted for 38% (178) of the cases. West Africa had the highest number of recorded cases with 179; the majority (162 cases) were caused by Histoplasma capsulatum var. dubuosii (Hcd). From the Southern African region, 150 cases have been reported, and the majority (119) were caused by H. capsulatum var. capsulatum (Hcc). There have been 12 histoplasmin skin test surveys with rates of 0% to 35% positivity. Most cases of Hcd presented as localised lesions in immunocompetent persons; however, it was disseminated in AIDS patients. Rapid diagnosis of histoplasmosis in Africa is only currently possible using microscopy; antigen testing and PCR are not available in most of Africa. Treatment requires amphotericin B and itraconazole, both of which are not licensed or available in several parts of Africa.

Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome.

Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections.

Immunologic studies of patients with histoplasmosis.

Immunologic responses of patients with active histoplasmosis (Group I) were compared to the responses of healthy persons with positive histoplasmin skin-test reactions (Group II), and to those of healthy persons with negative histoplasmin skin-test reactions (Group III). Cellular immune responses were significantly depressed in patients. Seven (54 per cent) of 13 patients failed to respond to histoplasmin skin testing, and two (15 per cent) failed to respond to skin-test antigens unrelated to Histoplasma capsulatum. Lymphocyte transformation (LT) responses of patients were severely depressed in vitro (p less than 0.001) to Histoplasma antigens when compared to the responses of healthy, histoplasmin-reactive donors. Transformation responses to Candida antigen were not impaired in the patient population. Culturing lymphocytes of patients in serum obtained from healthy donors as opposed to autologous serum resulted in a significant (p less than 0.05) increase in LT responses to H. capsulatum. Responses to Candida antigen and to mitogens were not affected by the serum source. Serum-mediated suppression of LT responses correlated (p less than 0.01) with complement-fixing antibody titers to Histoplasma yeast-phase antigen and suggests that antibody, either alone or complexed with antigen, may suppress T-cell response in vitro in this disease.

Brote de histoplasmosis en la Escuela de Cadetes de la Base Aérea de Morón, Provincia de Buenos Aires, República Argentina

A histoplasmosis outbreak affecting 6 previously healthy Air Force cadets is herein presented. The patients suffered from fever and respiratory symptoms after having cleaned an abandoned hangar soiled with pigeons and bat droppings. They all presented fever, myalgia, tachypnea, and nonproductive cough. Chest X-ray and CT scan studies showed disseminated reticulonodular images affecting both lungs. Hiliar adenomegalies were also observed. All patients achieved a favourable outcome without antifungal treatment. Both serologic tests searching for specificic antibodies (immunodiffusion and counterimmunoelectrophoresis) and histoplasmin skin tests were positive in all cases. Five soil samples mixed with pigeons and bat droppings were collected from the hangar. Suspensions of these samples were inoculated into 20 hamsters by intraperitoneal injection; mycelial phase of H. capsulatum was isolated from liver and spleen cultures. The genetic profile of this strain was compared with 12 isolates obtained from Argentinean patients, and a great degree of homogeneity was observed (> 96% similarity). Although histoplasmosis is endemic in the wet Pampas, this is the first epidemic outbreak reported south of the 34th parallel.

Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil

To identify the main clinical and laboratory features of disseminated histoplasmosis (DH) in human immunodeficiency virus (HIV) patients and compare them with those of HIV patients with other opportunistic diseases. Retrospective study of HIV patients comparing the clinical and laboratory data of patients with and without DH. Univariate and multivariate analyses were performed to verify the risk factors related to DH. In total, 378 HIV patients were included, 164 with DH and 214 with other opportunistic diseases. Acute renal failure, respiratory insufficiency and septic shock were more frequent in DH patients, who also had a higher mortality (32%vs. 14%, P < 0.001). Independent risk factors for DH were: acute renal failure [odds ratio (OR) 5.2; 95% confidence interval (CI) 3.2-8.5; P < 0.001], splenomegaly (OR 3.4; 95% CI 1.19-9.9; P < 0.001), respiratory insufficiency (OR 2.7 95% CI 1.5-5.0; P < 0.001), proteinuria (OR 2.7; 95% CI 1.3-5.2; P = 0.03), hypotension (OR 2.5; 95% CI 1.2-5.0; P = 0.008), hepatomegaly (OR 2.4; 95% CI 1.2-4.8; P = 0.01), cutaneous lesions (OR, 1.9; 95% CI 1.0-3.3; P = 0.02) and weight loss (OR 1.8; 95% CI 1.0-3.1; P = 0.03). Our results suggest that DH is a severe opportunistic disease with high mortality rate, which should be promptly recognized in order to provide early specific treatment.

Histoplasmosis infection in Spanish travelers to Latin America

The aim of the study presented here was to assess the incidence of histoplasma infection in a cohort of 342 individuals in Spain who had traveled to Latin America for the first time. The histoplasmin skin test was positive in 20% of the travelers, and Central America posed a higher risk for infection than South America (p=0.013). Sleeping outdoors (p=0.031) and the duration of travel (p=0.016) were also identified as significant risk factors. Serological testing demonstrated poor overall sensitivity for detecting infection in the travelers, but for the symptomatic acute cases the results were improved. Histoplasmosis must be considered in patients presenting with fever (odds ratio=3.51 [1.52-8.12]) or cough (odds ratio=4.24 [1.32-13.58]) after visiting Latin America. The results of this study have public health implications and indicate the risks of acquiring histoplasmosis should be included in pre-travel counseling.

Recurrent Exposure toHistoplasma capsulatumin Modern Air‐Conditioned Buildings

Between 1989 and 1996, an epidemic of histoplasmosis occurred on a medical school campus. There had been numerous construction projects on the campus that involved previously wooded land and were adjacent to a large bird sanctuary. We investigated the epidemic with active surveillance to detect cases, a histoplasmin skin-test survey, inspection of the air-filtration systems of the involved buildings, and cultures of soil samples. The investigation also included a simulation of entry into air-intakes of the buildings from spore sources by means of a wind-tunnel analysis of a model of the campus that used inert gas. After control procedures were instituted, sentinel population groups had follow-up with yearly serological tests. From 1989 through 1996, there were 29 cases of histoplasmosis that occurred among school employees. All cases with a defined onset began during periods of ongoing campus construction. Positivity rates for histoplasmin skin testing were higher among on-campus personnel (47%) than among off-campus employee control subjects (28%) (P<.001); the rates were highest in employees who worked on the upper floors of 2 research buildings. The air-handling units on the roofs of these buildings were not designed to exclude Histoplasma spores. The wind-tunnel experiment indicated that spores aerosolized in the bird sanctuary were not taken into campus buildings. The major sources of employee exposure to H. capsulatum spores were the construction sites. Low-level, recurrent exposures occurred over several years inside modern research buildings. This phenomenon, which has not been previously described, may play a role in the epidemiology of spore-transmitted diseases in urban settings.

PARACOCCIDIOIDOMYCOSIS: AN EPIDEMIOLOGIC SURVEY IN A PEDIATRIC POPULATION FROM THE BRAZILIAN AMAZON USING SKIN TESTS

Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis. The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 x 10(-4) for each). Overall prevalence was 4.6% (95% confidence interval = 2.5-7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.

Incidence of histoplasmin hypersensitivity in the Philippines.

Long-term residents of the Philippines were skin tested with histoplasmin skin test material. This study was conducted with 143 electric company (MERALCO) employees from Manila, Philippines. We found that 37 (26%) of the subjects were skin test positive. Characteristics of the positive group were: average age of 37 years; all except one were lifelong inhabitants of Metro Manila; 25 were male and 12 were female; one-half of the subjects reported extended contact with chickens. Despite these findings, histoplasmosis is considered to be a very rare disease in the Philippines. This survey indicates that Histoplasma capsulatum is sufficiently present in the Philippines to come in contact with one-fourth of the test population. This reinforces the hypothesis that histoplasmosis is present in the Philippines and is probably being misdiagnosed as granulomatous-inducing diseases such as tuberculosis, e.g., so-called "drug resistant" tuberculosis. We recommend larger surveys of this type and attempts to culture the etiologic agent from natural sources such as chicken and bat droppings.

Brote de histoplasmosis aguda en viajeros chilenos a la selva ecuatoriana: un ejemplo de Medicina Geográfica

Eight Chilean teenagers traveled to Ecuador in January 1999, where they were bitten by mosquitoes, had contact with parakeets and lodged in poorly hygienic places; 6/8 visited for 5-10 minutes the interior of a bat cave. About a week later these 6 began with headache, myalgia and fever that lasted 2-3 weeks. 5/6 had dry cough with no respiratory distress. The index case was seen in the 2nd week of symptoms. A chest x-ray showed multiple nodular infiltrates as in the other five. Two had histoplasma serology, one was negative and the other positive at a low titer; histoplasmin skin test showed induration of 17-27 mm in all six. An acute histoplasmosis with massive exposure was diagnosed and treated with itraconazole for 3 weeks. All became asymptomatic and chest x-rays returned to normal. Histoplasmosis (non existent endogenously in Chile) is, among other geographic and tropical diseases, a risk for Chilean travelers. Awareness of this in the general population and development of expertise in these diseases by local health care providers is required.

Outbreak of histoplasmosis among cavers attending the National Speleological Society Annual Convention, Texas, 1994.

In June 1994, 18 people developed serologically confirmed histoplasmosis following cave exploration associated with the annual National Speleological Society Convention in Bracketville, Texas. Six others had an undiagnosed illness suspected to be histoplasmosis. Two persons were hospitalized. We conducted a survey of convention attendees and a nested case-control study of those entering caves. We also conducted a histoplasmin skin test survey of a subgroup of the society, the Texas Cavers Association, who were attending a reunion in October 1994. Among the national convention attendees, exposure to two caves was identified as responsible for 22 (92%) of the 24 cases; 12 (75%) of 16 people exploring one cave (Cave A) and 10 (77%) of 13 exploring a separate cave (Cave B) developed acute histoplasmosis. Additional risk-factors included fewer years of caving experience, longer time spent in the caves, and entering a confined crawl space in Cave A. Of 113 participants in the separate skin test survey, 68 (60%) were found to be skin test positive, indicating previous exposure to Histoplasma capsulatum. A positive skin test was significantly associated with male sex and more years of caving experience. Those less experienced in caving associations should be taught about histoplasmosis, and health care providers should pursue histories of cave exposure for patients with bronchitis or pneumonia that does not respond to initial antibiotic therapy.

Commentary on histoplasmosis

Click to increase image sizeClick to decrease image sizeKey Words: Presumed ocular histoplasmosisHistoplasma capsulatum; fungal infectionchoroiditis

Immunologic, genetic and social human risk factors associated to histoplasmosis: studies in the State of Guerrero, Mexico.

Immunologic and occupational aspects of the susceptible population exposed to Histoplasma capsulatum, the causative agent of histoplasmosis were analyzed in the Mexican State of Guerrero. Three areas were studied, Juxtlahuaca, Olinala, and Coyuca; in the first two, their populations refer contact with bat guano and/or avian excreta, which contain nutrients for fungal growth, while the Coyuca population referred no contact with the above mentioned excreta. Previous infection with H. capsulatum was determined by histoplasmin-skin test, and the response was higher in men than in women (93.87, 85.71, and 6.6% for men, and 78.94, 66.6, and 0% for women) in Juxtlahuaca, Olinala, and Coyuca, respectively. Labor activities related to a persistent contact with the fungus were considered as an occupational risk factor, histoplasmin-skin test reached 88.57 and 36.36% of positive response in individuals with high and low risk activities. A high percentage of histoplasmin responses was observed in subjects with constant contact with H. capsulatum, such as, cave-tourist guides, peasants, and game-cock handlers, and generally they developed the largest diameter of skin reactions. Genetic risk factor was determined by studying the gene frequency of the Major Histocompatibility Complex antigens in a sample of individuals and their degree relatives in Juxtlahuaca, Olinala, and Coyuca. Significant differences were found for HLA-B22 and B17 antigens in Juxtlahuaca, and for HLA-B22 in Olinala, in comparison to the usual gene frequency observed in the normal Mexican population. HLA results were important, considering that HLA-B22 was previously found to be possibly related to pulmonary histoplasmosis in Guerrero.

Histoplasmin and paracoccidioidin skin reactivity in infantile population of northern Argentina (1).

In order to estimate ages at which etiological agents of systemic mycoses initiate infection, histoplasmin and paracoccidioidin skin tests were performed in 344 children of both sexes, between 2 and 15 years old. They were selected from a statistically significant population sample Gral. San Martín city (Northeast Argentina). Tests were read 48 h after injection and considered positive if a 5 mm on larger induration was present. Circulating antibodies were also evaluated by agar gel immunodiffusion. The overall infection rate for H. capsulatum was 9.2%, belonging to children from 4 to 14 years old, without significant differences among sexes. Five children from 2 to 14 years old were positive to paracoccidioidin (1.6%). None of the children had specific antibodies neither signs of active mycosis. Results show H. capsulatum infection can be found from age 4, while for P. brasiliensis the lower limit was two years old. These findings may contribute to better knowledge on infantile fungal infection in a geographical region where no previous references can be found.

Disseminated Histoplasmosis in Persons Infected with Human Immunodeficiency Virus

Disseminated histoplasmosis is an AIDS-defining illness that occurs in about 5% of AIDS patients residing in histoplasmosis-endemic areas of the United States (the Mississippi and Ohio river valleys). This disease develops as a result of acute infection and perhaps also as the result of reactivation of latent infection: cases reported from areas such as New York City, where histoplasmosis is not endemic, are most likely due to reactivation of an infection acquired earlier in a histoplasmosis-endemic area, while cases in histoplasmosis-endemic areas are most likely due to acute infection, especially in outbreak settings. Disseminated histoplasmosis in HIV-infected patients is usually associated with advanced immunosuppression, with CD4+ lymphocyte counts of < 75/mm3. Currently, histoplasmin skin testing of HIV-infected patients does not seem to be useful in detecting previous exposure and therefore is not helpful in identifying groups of patients who are at risk for dissemination and who should be targeted for preventive efforts. The current public health recommendation for HIV-infected patients is to avoid exposure to sites likely to harbor high levels of Histoplasma capsulatum, such as chicken coops and bird roosts. The role of chemoprophylaxis is not clear, but an ongoing study by the Mycoses Study Group is evaluating the role of prophylactic itraconazole. If strategies for the prevention of disseminated histoplasmosis in HIV-infected patients are to be improved, studies must better define the risk factors for this opportunistic infection, describe its natural history, and develop more reliable tests to predict its development.

Histoplasmosis during childhood.

To define the clinical presentation of histoplasmosis among hospitalized children, we reviewed the charts of patients treated for histoplasmosis at Vanderbilt University Children's Hospital during the years 1968 through 1988. Thirty-five patients with histoplasmosis diagnosed by culture, pathologic examination, or serologic testing were identified, including 29 patients (83%) with pulmonary/mediastinal infection, 5 (14%) with disseminated disease, and 1 (3%) with primary cutaneous histoplasmosis. The most common symptoms included fever, present in 26 patients (74%), and cough, present in 20 (57%). Of 26 patients with fever, 18 (69%) had fever of > 2 weeks' duration and 7 (27%) had temperatures > or = 40.5 degrees C (> or = 105 degrees F). Abnormal physical findings were few, but 19 patients (54%) had wheezing. Chest radiographs were obtained in all cases except one; 31 (91%) showed abnormalities, including adenopathy in 25 cases (74%) and infiltrates in 19 (56%). Histoplasmin skin tests were positive for 22 (96%) of the 23 patients tested. No cases of classic disseminated histoplasmosis of infancy were identified. Histoplasmosis should be considered in the differential diagnosis when children living in endemic areas are evaluated for persistent fever, cough, and/or wheezing, particularly if adenopathy is seen on the chest radiograph.