• 1.

    CDC, 1987. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of state and territorial epidemiologists; AIDS program, center for infectious diseases. MMWR Suppl 36: 1S15S.

    • Search Google Scholar
    • Export Citation
  • 2.

    Adenis AA, Valdes A, Cropet C, McCotter OZ, Derado G, Couppie P, Chiller T, Nacher M, 2018. Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis 18: 11501159.

    • Search Google Scholar
    • Export Citation
  • 3.

    Wheat LJ, Batteiger BE, Sathapatayavongs B, 1990. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore) 69: 244260.

    • Search Google Scholar
    • Export Citation
  • 4.

    Wheat J 2018. Central nervous system histoplasmosis: multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine (Baltimore) 97: e0245.

    • Search Google Scholar
    • Export Citation
  • 5.

    Wheat LJ, Connolly-Stringfield PA, Baker RL, Curfman MF, Eads ME, Israel KS, Norris SA, Webb DH, Zeckel ML, 1990. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) 69: 361374.

    • Search Google Scholar
    • Export Citation
  • 6.

    Riddell Jt, Wheat LJ, 2019. Central nervous system infection with Histoplasma capsulatum. J Fungi (Basel) 5: 70.

  • 7.

    Nacher M, Adenis A, Guarmit B, Lucarelli A, Blanchet D, Demar M, Djossou F, Abboud P, Epelboin L, Couppié P, 2020. What is AIDS in the Amazon and the Guianas in the 90-90-90 era? PLoS One 15: e0236368.

    • Search Google Scholar
    • Export Citation
  • 8.

    Nacher M 2020. Disseminated histoplasmosis in HIV-infected patients: a description of 34 years of clinical and therapeutic practice. J Fungi (Basel) 6: 164.

    • Search Google Scholar
    • Export Citation
  • 9.

    Donnelly JP 2020. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis 71: 13671376.

    • Search Google Scholar
    • Export Citation
  • 10.

    Grabar S, Le Moing V, Goujard C, Leport C, Kazatchkine MD, Costagliola D, Weiss L, 2000. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 133: 401410.

    • Search Google Scholar
    • Export Citation
  • 11.

    Dione A 2015. Méningo-encéphalite à Histoplasma capsulatum chez une patiente infectée par le VIH: une pathologie à évoquer chez les patients vivant en Amérique latine ou en revenant. La Lettre de l’Infectiologue 5: 194195.

    • Search Google Scholar
    • Export Citation
  • 12.

    Nacher M 2018. Histoplasma capsulatum antigen detection tests as an essential diagnostic tool for patients with advanced HIV disease in low and middle income countries: a systematic review of diagnostic accuracy studies. PLoS Negl Trop Dis 12: e0006802.

    • Search Google Scholar
    • Export Citation
  • 13.

    Pan American Health Organization, World Health Organization, 2020. Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV. Washington, DC and Geneva, Switzerland: Pan American Health Organization and World Health Organization, 156.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Histoplasmosis of the Central Nervous System: A Case Series between 1990 and 2019 in French Guiana

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  • 1 Infectious Diseases Department, Centre Hospitalier de Cayenne, Cayenne, French Guiana;
  • 2 CIC INSERM 1424, Centre Hospitalier de Cayenne, Cayenne, French Guiana;
  • 3 Ecosystèmes Amazoniens et Pathologie Tropicale, EA3593, Université de Guyane, Cayenne, French Guiana;
  • 4 Centre Gratuit D’Information de Dépistage et de Diagnostic, Centre Hospitalier Agen Nerac - Hôpital Saint-Esprit, Agen, France;
  • 5 Université Paris Descartes, Centre D’Infectiologie Necker Pasteur, IHU Imagine, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France;
  • 6 Laboratory of Parasitology and Mycology, University of French Guiana, Cayenne, French Guiana;
  • 7 Health Centres for Remote Areas, Andrée Rosemon Hospital, Cayenne, French Guiana;
  • 8 Dermatology Department, Andrée Rosemon Hospital, Cayenne, French Guiana

Abstract.

Disseminated histoplasmosis is the most frequent acquired immunodeficiency syndrome–defining illness in French Guiana. Paradoxically, central nervous system (CNS) involvement has been scarcely described. We aimed to identify CNS histoplasmosis in our territory. We conducted an observational, multicentric, descriptive, and retrospective study including patients with proven or probable CNS histoplasmosis according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MGS). The study population consisted of patients admitted in one of the hospitals of French Guiana between January 1, 1990 and December 31, 2019. During the study period, 390 cases of HIV-associated histoplasmosis were recorded, in which six of them had CNS infections with Histoplasma capsulatum. The male to female sex ratio was 0.25, and the median age at diagnosis was 37.5 years. The median CD4 count was 42 cells/mm3 ([IQR: 29–60]). All patients had disseminated histoplasmosis. Usual signs of meningitis were observed in three patients and focal signs in four patients. One patient had no neurological signs. The median time between the first cerebral symptoms and diagnosis was 22.4 days (IQR 9.5–36.2). Two patients died within a month after diagnosis. In conclusion, few proven CNS localizations of histoplasmosis were observed on 30-year study in French Guiana. This low proportion suggests that the documentation of CNS involvement is often not ascertained for lack of awareness of this particular presentation, and for lack of rapid and sensitive diagnostic tools.

INTRODUCTION

Progressive disseminated histoplasmosis has been an AIDS-defining infection since 1987.1 In Latin America, it is considered as one of the most common yet often undiagnosed opportunistic infection of persons with advanced HIV.2 As the level of immunity declines, the fungal dissemination worsens, which leads to polymorphous nonspecific manifestations that often involve the lungs, bone marrow, liver, lymph nodes, digestive system, skin, mucosa, genitourinary tract, adrenal glands, bones, joints, etc. Central nervous system (CNS) infection is rarely described. In the 1950s, autopsy studies proved the dissemination of histoplasmosis infection to the CNS. In that study, only two of six patients had had signs of meningitis. Its prevalence has, however, been estimated to concern 5–10% of the patients with disseminated histoplasmosis.3 Symptoms are classically subacute over several weeks, with only a quarter of patients having had symptoms for less than a month. The most common manifestations are headaches (60%), altered mental status (42%), focal neurological deficits (30%), cognitive deficits, seizures, and chronic meningitis (39%).4

In 60% of cases, the diagnosis of chronic Histoplasma meningitis is often delayed by over 1 month, mostly because physicians overlooked the diagnosis. However, more recently, in the United States, the use of Histoplasma antigen detection or anti-Histoplasma antibody detection in the cerebrospinal fluid (CSF) has led to earlier diagnoses. Whereas the relapse rate and mortality of CNS histoplasmosis used to be very high5—often presenting as meningitis in severely immunocompromised patients with poor compliance—antifungal therapy has transformed this universally fatal illness to a manageable condition, if diagnosed and treated early.6

H. capsulatum is endemic in French Guiana.7,8 In this region, disseminated histoplasmosis is the most frequent AIDS-defining illness.7 Although physicians are prompt to think about the diagnosis in most cases, and direct examination and culture are available, up-to-date antibody and antigen detection tests are still not routinely available and practiced in the CSF of people living with HIV in French Guiana. Few data regarding CNS histoplasmosis in persons living with HIV are available in the Amazon region. Our objective was thus to document all the cases of CNS histoplasmosis that occurred in our hospital during the last 30 years.

METHODS

Study type.

The study was observational, multicentric, descriptive, and retrospective.

Study site.

The study involved the hospital wards caring for HIV-infected patients requiring hospitalization in the three hospitals of our French Territory of America (Cayenne, Kourou, and Saint Laurent du Maroni).

Study population.

The source population consisted of people living with HIV hospitalized for an episode of histoplasmosis between January 1, 1990 and December 31, 2019. Patients were identified through the retrospective cohort of the French Hospital Database on HIV. The target population consisted of patients having presented with H. capsulatum infection of the CNS during their hospital stay.

Cases were classified as proven or probable CNS histoplasmosis according to the EORTC/MGS criteria (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group). The criteria for proven histoplasmosis were histopathology or direct microscopy on specimens obtained from an affected site showing the distinctive form of the fungus, recovery by culture of the fungus, or blood culture that yields the fungus; criteria for probable invasive histoplasmosis were evidence for geographical or occupational exposure (including remote) to the fungus and compatible clinical illness and Histoplasma antigen in urine, serum, or body fluid.9 A patient with a positive PCR in the CSF was considered as a putative case. We collected clinical, biological, and radiological data from medical records.

All adults (> 18 years of age) living with HIV with a CNS sample positive for H. capsulatum on direct examination and/or culture and/or PCR were included.

Data collection.

CNS histoplasmosis cases were identified from the database of the laboratory that identified positive CSF samples by mycological or PCR examination. The database of the medical information department of the three hospitals was also queried. For included patients, data were retrospectively collected in the three hospitals of French Guiana from patients’ medical records. Data collection included sociodemographic variables (gender, age, and country of birth), medical data (including general condition, fever, pulmonary signs, digestive signs, and lymphadenopathies), imagery data (brain computed tomography [CT] scan and magnetic resonance imaging [MRI]), routine blood count and CSF results, microbiological data (direct examination, culture, pathology, and PCR), immuno-virological data (CD4 and CD8 counts, and HIV viral load before antiretroviral therapy and at the time of H. capsulatum infection), therapeutic data (antifungals, antibiotics, corticosteroids, antiretrovirals...), and the last consultation date after the considered H. capsulatum infection.

Statistical analysis.

The data from the study were analyzed using Microsoft Excel 2013. Descriptive analysis allowed describing sociodemographic, clinical, immuno-virological, and therapeutic data. Means and SDs, or medians and interquartile ranges were used depending on variable distribution.

Ethical and regulatory aspects.

All HIV-infected patients followed at Cayenne Hospital are included in the DAT'AIDS database. DAT'AIDS (www.dataids.org) is a nonprofit organization created in 2006 around a Scientific Council aiming to compile and analyze databases on HIV, HBV, HCV, STI, and associated pathologies. Data are routinely entered by physicians and research technicians through the eNADIS® computerized medical records. These medical records are used for the management of patients suffering from a chronic pathology, mainly HIV and viral hepatitis. This database is part of the French Hospital Database on HIV, a national retrospective cohort which was described elsewhere.10 This database received approval from the Commission Nationale Informatique et Libertés since November 27, 1991. All included patients signed an informed consent form.

RESULTS

During the 30-year study period, 390 cases of HIV-associated histoplasmosis were recorded in our database. Among them, we identified six CNS infections with H. capsulatum (1.5% [95% CI: 0.5–3.3]). Five cases were confirmed cases, and one was probable. Between 2011 and 2019, only one patient with CNS histoplasmosis was identified. The clinical characteristics of the patients are summarized in Table 1. All patients came from endemic areas (two from Haiti, one from Brazil, one from French Guiana, one from Guyana, and one from Suriname). Four were women (sex ratio M:F 0.25), and the median age at diagnosis was 38 years (IQR: 35–45) (Table 2). All had a CD4 count of less than 150 cells/mm3 (median CD4 count: 42 cells/mm3 [IQR: 29–61]). It was their first episode of histoplasmosis, and no patient was receiving histoplasmosis primary prophylaxis using itraconazole. Diagnosis of HIV infection was already known for all the patients, and three of them were treated: one had been treated by highly active antiretroviral therapy (HAART) for 6 months apparently with good compliance, but the other two had stopped their treatment (Table 3).

Table 1

Summary of the cases

Case123456
Age (years) gender33 Female36 Female47 Male35 Male48 Female39 Female
Country of birthHaitiHaitiGuyanaSurinameFrench GuianaBrazil
Year of the onset of symptoms199319982007200820092014
Delay between diagnoses of HIV and cerebral histoplasmosis (month)5257018486
Duration between 1st symptoms and diagnosis (days)1798072839
CD4 count (cells/mm3)29622976556
HIV RNA (copies/mL)UKUKUK687,00059,894147,615
HAART at presentationNoNoNoYes but nonobservant: ritonavir, fosamprenavir, abacavir, and lamivudineYes but nonobservant: zidovudine, lamivudine, lopinavir, and ritonavirTenofovir, lamivudine, and efavirenz
CoinfectionHCVHCVNoneNoneNoneNone
Opportunistic diseasesNoNoCerebral toxoplasmosis and pulmonary TBOral candidiasisNoCMV viremia and pulmonary TB
Non-CNS symptoms (duration)Fever, diarrhea, and short breath (12 weeks)Fever and splenomegaly (2 weeks)Weight lost, cough, and diffuse lymphadenopathy (12 weeks)Weight lost, fever, abdominal pain, vomiting, and bronchial rattel (12 weeks)Weight lost, dyspnea, cough, expectoration, and otomastoiditisFever, abdominal pain, nausea, vomiting, diarrhea, and cough (20 weeks)
CNS symptoms (duration)MeningoencephalitisMeningeal syndrome, and headaches (2 weeks)Headaches, ideomotor slowdown, and focal deficitNoAtaxiaHeadaches, confusion, temporospatial disorientation, meningeal syndrome, and dysarthria (2 weeks)
ImagingChest X-RAY = interstitial syndromeChest X-RAY = right upper lobe opacity sequelae of tuberculosisBrain CT scan = edema and parenchymatous lesions in the cockadeBrain CT scan = normalBrain CT scan = normalBrain CT scan = hypodense gaps of the left internal capsule
Abdominal US = normalAb echo = splenomegaly and lymphadenopathy
Brain CT scan = not performedBrain CT scan = hydrocephalusMRI = hypersignals of the region of the central gray nuclei in injected T1 and FLAIR
CSF analysisUKWBC: 71WBC: 20 (% P: 5, L: 95)WBC: 1WBC: 44 (%P: 25, L: 75)WBC: 11
PR: 0.98 g/LPR: 1,4 g/LPR: 0.3 g/LPR: 1.7 g/LPR: 0.72 g/L
GLU: 2.2 mmoL/LGLU: 2.9 mmoL/LGLU: 2.8 mmol/LGLU: unknownGLU: 1.2 mM
CSF culturePositivePositiveNegativePositivePositivePositive
Other positive culture to H. capsulatumBone marrow BloodBone marrowBone marrowBone marrowBone marrowBone marrow Blood
PCR on CSFNot performedNot performedPositiveNegativeNegativeNot performed
Anti-TB treatment initiated before histoplasmosis diagnosisYesYesNoNoNoYes
TreatmentIV AmBOral itraconazoleIV L-AmB for 7 days and then oral itraconazoleItraconazoleIV L-AmBIV AmB for 1 day and then oral itraconazole
Modified HAART regimenZidovudineNoNoRitonavir, fosamprenavir, lamivudine, and abacavirDidanosine, zidovudine, ritonavir, and lopinavirTénofovir, emtricitabine, and efavirenz
28-Day deathYesNoNoNoYesNo
Outcome (month)1889653078

CMV = cytomegalovirus; CSH = cerebrospinal fluid; IV = intravenous; GLU = glycorrhachia; HAART = highly active antiretroviral therapy; L = lymphocytes; L-AmB = liposomal amphotericin B; MRI = magnetic resonance imaging; P = polynuclear neutrophils; PR = proteinorrachia, TB = tuberculosis; UK = unknown; WBC = white blood cells.

Table 2

Summary of the main continuous variables of the six patients and comparison to the French Guiana histoplasmosis cohort

Continuous variableCentral nervous system histoplasmosis, 1990–2019 (N = 6)Disseminated histoplasmosis, 1990–2019 (N = 279)
MedianIQR: 25–75RangeMedianIQR: 25–75RangeN
Age (years)3835–4533–483934–4619–68279
Duration between first symptoms and diagnosis (days)2310–361–69NANANANA
Viral load147,615103.755–417,30859,894–687,000385,00098,487–62371566–8200,00052
CD44229–617–653212–720–550274
Delay between diagnoses of HIV and cerebral histoplasmosis (month)339–510–57240–720–252220
Table 3

Summary of the main categorical variable of the six patients and comparison to the French Guiana histoplasmosis cohort

Categorical variablesCentral nervous system histoplasmosis, 1990–2019 (N = 6), n (%)Disseminated histoplasmosis, 1990–2019 (N = 279), n (%)
Male gender2 (33)184 (66.0)
Highly active antiretroviral therapy at the diagnosis3 (50)28 (10.0)
28-Day death2 (33)35 (12.5)

All patients had disseminated histoplasmosis, with a positive bone marrow culture for 5/5 of them and positive blood cultures for two of them.

Two of them had a coinfection with hepatitis C virus, and four of them had another opportunistic infection (tuberculosis, the Epstein–Barr virus, Cytomegalovirus, and cerebral toxoplasmosis).

Usual signs of meningitis including headache, nuchal rigidity, and fever were observed in three of six patients. A focal sign (such as motor deficit or ataxia) was observed in four patients. One patient had no neurological signs. The median time between the first cerebral symptoms and diagnosis was 23 days (IQR: 10–36). Five of six CSF culture were positive. The remaining case was diagnosed by PCR in the CSF. Bone marrow was positive in mycological culture for all patients and blood culture for two patients. Biochemical characteristics of the CSF were available for five patients. Four of five had biological meningitis with lymphocytic predominance, hyperproteinorrachia, and hypoglycorrhachia. The median hemoglobin level was 89 g/L (86–104), and the median neutrophil count was 1.7 G/L (1.6–1.9). Beta-D-glucan was only performed in patient #6 supported in 2014, and the level was 412 pg/mL (normal < 80). Galactomannan antigen detection was performed in none of them.

Five patients had a cerebral imaging (among the five patients with CT scan, one also had an MRI): two patients presented a hydrocephaly, and one had parenchymal lesions compatible with fungal abscesses. Two patients had a normal cerebral scan. MRI was performed in one patient with hypersignals of the region of the basal ganglia in injected T1 and FLAIR. Antituberculosis treatment was started for three of the six patients before obtaining the mycological diagnosis.

Three patients were treated with liposomal amphotericin B (L-Amb), one with deoxycholate amphotericin B, and two with itraconazole as a first-line treatment. One patient was switched from L-Amb to itraconazole after 1 week because of poor tolerance. The duration of treatment is not known. No surgical intervention was performed.

Zidovudine was introduced for the patient treated in 1993, which did not prevent his death. Highly active antiretroviral therapy was modified for patients 4, 5, and 6, but this did not prevent the death of the first two patients, which was not due to an immune reconstitution inflammatory syndrome (IRIS). Patient 6 did not develop IRIS and is still alive 5 years after her management, with immuno-virological success, but a persistent neurological symptomatology—such as headache—and abnormal CSF with a proteinorachy between 1 and 1.5 g/L and a cellulorachy around 30 cells per mm3, predominantly lymphocytic, without any other infectious cause was found, despite extensive explorations.

Two patients died within a month after diagnosis, and two others died from a bacterial infection 4 and 7 years after diagnosis, respectively. One patient remained with persistent headaches and CSF abnormalities for several years despite persistent immune restoration.11 Two patients were still alive at the time this manuscript was written.

DISCUSSION

We report six cases of CNS histoplasmosis in HIV-infected patients in French Guiana. This represents 1.5% of disseminated cases over the study period, which is far lower than what was reported in the United States. The most likely explanation for our observation is that, despite the fact that physicians are quite aware of the major importance of H. capsulatum among opportunistic infections, diagnosis is still difficult in the absence of valuable diagnostic methods such as antigen detection, serodiagnosis, or PCR in the CSF.12 Neurological signs are nonspecific and may not be on the forefront of the clinical presentation and may even be absent. Cerebrospinal fluid analysis can be normal in highly immunocompromised patients. CNS histoplasmosis should be considered as a serious differential diagnosis of CNS tuberculosis, which is one of the main causes of CNS involvement in AIDS. One of our patients had no clinical signs of meningitis, a normal CSF white blood cell count, and a normal cerebral CT scan. Fungal culture from CSF has poor sensitivity, and it is slow, thus delaying the onset of treatment. PCR is a useful tool, allowing earlier diagnosis in this life-threatening disease, but it is not always performed. Diagnostic delay is an important obstacle for optimal treatment of CNS histoplasmosis. A complementary explanation of the low prevalence may be that when the diagnosis of disseminated is performed from samples from another organ (bone marrow, biopsies…), treatment is often already presumptively given, or is promptly started, and the exhaustive list of the dissemination sites may seem to be relatively trivial compared with the diagnosis itself. However, this is not true for CNS involvement because of the therapeutic repercussions of this specific site infection. Recommendations suggest liposomal AmB 5 mg/kg/day should be given for up to 4–6 weeks as tolerated, followed by oral itraconazole for at least 12 months. Because of the possibility of relapses, CSF parameters should be reevaluated before discontinuation of itraconazole at 12 months to verify that cell counts are normal and, when possible, that Histoplasma antigen is absent from the CSF. When the CNS involvement is not known, transition from L-Amb to itraconazole, and then itraconazole interruption may be accelerated, thus leading to suboptimal treatment of the CNS infection.6

Although it has been suggested that there are genetic and phenotypic differences between H. capsulatum clades in the United States and South America, we do not believe our observation reflects virulence differences.

In conclusion, we observed few proven CNS localizations in French Guiana. This low proportion suggests that the documentation of CNS involvement is often not ascertained for lack of awareness of this particular presentation, and for lack of rapid and sensitive diagnostic tools. This leads to suboptimal treatment strategies that treat disseminated histoplasmosis without taking into account the requirements of the neurological dissemination. Hence, although clinicians are very aware of the importance of disseminated histoplasmosis in French Guiana, there is still a margin of progress, which reemphasizes the need for antigen detection tests in all countries where H. capsulatum is endemic.13 In front of a clinical picture of subacute or chronic encephalitis in a person living with HIV, one should evocate the diagnosis of histoplasmosis of the CNS, as a possible differential diagnosis of tuberculosis of the CNS.

REFERENCES

  • 1.

    CDC, 1987. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of state and territorial epidemiologists; AIDS program, center for infectious diseases. MMWR Suppl 36: 1S15S.

    • Search Google Scholar
    • Export Citation
  • 2.

    Adenis AA, Valdes A, Cropet C, McCotter OZ, Derado G, Couppie P, Chiller T, Nacher M, 2018. Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis 18: 11501159.

    • Search Google Scholar
    • Export Citation
  • 3.

    Wheat LJ, Batteiger BE, Sathapatayavongs B, 1990. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore) 69: 244260.

    • Search Google Scholar
    • Export Citation
  • 4.

    Wheat J 2018. Central nervous system histoplasmosis: multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine (Baltimore) 97: e0245.

    • Search Google Scholar
    • Export Citation
  • 5.

    Wheat LJ, Connolly-Stringfield PA, Baker RL, Curfman MF, Eads ME, Israel KS, Norris SA, Webb DH, Zeckel ML, 1990. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) 69: 361374.

    • Search Google Scholar
    • Export Citation
  • 6.

    Riddell Jt, Wheat LJ, 2019. Central nervous system infection with Histoplasma capsulatum. J Fungi (Basel) 5: 70.

  • 7.

    Nacher M, Adenis A, Guarmit B, Lucarelli A, Blanchet D, Demar M, Djossou F, Abboud P, Epelboin L, Couppié P, 2020. What is AIDS in the Amazon and the Guianas in the 90-90-90 era? PLoS One 15: e0236368.

    • Search Google Scholar
    • Export Citation
  • 8.

    Nacher M 2020. Disseminated histoplasmosis in HIV-infected patients: a description of 34 years of clinical and therapeutic practice. J Fungi (Basel) 6: 164.

    • Search Google Scholar
    • Export Citation
  • 9.

    Donnelly JP 2020. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis 71: 13671376.

    • Search Google Scholar
    • Export Citation
  • 10.

    Grabar S, Le Moing V, Goujard C, Leport C, Kazatchkine MD, Costagliola D, Weiss L, 2000. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 133: 401410.

    • Search Google Scholar
    • Export Citation
  • 11.

    Dione A 2015. Méningo-encéphalite à Histoplasma capsulatum chez une patiente infectée par le VIH: une pathologie à évoquer chez les patients vivant en Amérique latine ou en revenant. La Lettre de l’Infectiologue 5: 194195.

    • Search Google Scholar
    • Export Citation
  • 12.

    Nacher M 2018. Histoplasma capsulatum antigen detection tests as an essential diagnostic tool for patients with advanced HIV disease in low and middle income countries: a systematic review of diagnostic accuracy studies. PLoS Negl Trop Dis 12: e0006802.

    • Search Google Scholar
    • Export Citation
  • 13.

    Pan American Health Organization, World Health Organization, 2020. Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV. Washington, DC and Geneva, Switzerland: Pan American Health Organization and World Health Organization, 156.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Loïc Epelboin, Centre Hospitalier Andrée Rosemon, Infectious and Tropical Diseases Department, Av des Flamboyants, Cayenne 97306, French Guiana. E-mail: loic.epelboin@ch-cayenne.fr

Authors’ addresses: Loïc Epelboin, Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana, and EA 3593 Team, Ecosystèmes amazoniens et pathologie tropicale, Université de la Guyane, Cayenne, French Guiana, E-mail: epelboincrh@hotmail.fr. Aïda Dione and Bastien Bidaud, Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana, E-mail: bastien.bidaud@gmail.com. Alexandra Serris, Centre d’Infectiologie Necker Pasteur, IHU Imagine, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris 5 Descartes, Paris, France, E-mail: alexandra.serris@gmail.com. Denis Blanchet, Centre Hospitalier Andree Rosemon, Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Cayenne, French Guiana, and EA 3593 EPAT Ecosystèmes Amazoniens et Pathologies Tropicales, Universite de la Guyane, Cayenne, French Guiana, E-mail: denis.blanchet@ch-cayenne.fr. Gaelle Walter, Unite des Maladies infectieuses et tropicales, Cayenne General Hospital, Cayenne, French Guiana, E-mail: gaelle.walter@ch-cayenne.fr. Gaelle Walter, Unite des Maladies infectieuses et tropicales, Cayenne General Hospital, Cayenne, French Guiana, E-mail: gaelle.walter@ch-cayenne.fr. Philippe Abboud, Emilie Mosnier, and Felix djossou, Department of infectious diseases, Cayenne General Hospital, Cayenne, French Guiana, E-mails: philippe.abboud@ch-cayenne.fr, emilie.mosnier@ch-cayenne.fr, and felix.djossou@ch-cayenne.fr. Mélanie Gaillet and Céline Michaud, Pôle des Centres Délocalisés de Prévention et de Soins, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana, E-mails: melanie.gaillet@ch-cayenne.fr and celine.michaud@ch-cayenne.fr. Pierre Couppie, EA3593 EPAT Epidémiologie des parasitoses et mycoses tropicales, Université des Antilles et de la Guyane, Cayenne, French Guiana, E-mail: pierre.couppie@ch-cayenne.fr. Magalie Demar, Centre Hospitalier Andrée Rosemon, Laboratory of Parasitology and Mycology, Cayenne, French Guiana, and EA3593 EPAT Epidémiologie des parasitoses et mycoses tropicales, Université des Antilles et de la Guyane, Cayenne, French Guiana, E-mail: magalie.demar@ch-cayenne.fr. Mathieu Nacher, EA3593 EPAT Epidémiologie des parasitoses et mycoses tropicales, Université des Antilles et de la Guyane, Cayenne, French Guiana, and Centre d’Investigation Clinique Epidémiologie Clinique Antilles Guyane CIC-EC INSERM CIE 802, Cayenne General Hospital, Cayenne, French Guiana, E-mail: mathieu.nacher@ch-cayenne.fr. Antoine Adenis, Department of Internal Medicine, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana, E-mail: antoine.adenis@ch-cayenne.fr

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