Disseminated Histoplasmosis: Fighting a neglected killer of patients with advanced HIV disease in Latin America

Background: Histoplasmosis is a neglected acquired immune deficiency syndrome (AIDS)-defining disease in sub-Saharan African countries, which is commonly misdiagnosed as tuberculosis (TB) due to similar imagery and clinical features; patients usually receive presumptive anti-TB treatment that is considered as anti-TB treatment failure. Patients with advanced human immunodeficiency virus (HIV) disease (AHD), CD4<200/mm3 or World Health Organisation clinical stage 3 or 4, develop disseminated histoplasmosis (DH) diagnosed at a late stage or at post-mortem, owing to poor clinical suspicion, lack of rapid diagnosis tools to offer rapid and accurate results, and non-availability and accessibility of appropriate antifungal medications. We report 31 cases of DH amongst patients with AHD in sub-Saharan African population from the literature, highlighting the challenging care issue in sub-Saharan Africa. Results: Out of 31 reported cases 64.51% (20/31) were caused by Histoplasma capsulatum var capsulatum, 48.38% (15/31) being immigrants in Europe, Canada and Japan, with 41.93% (13/31) mortality, and 6 cases having no reported outcome. The poor index of suspicion on the part of clinicians; the lack of skilled laboratory personnel and rapid and accurate diagnosis tools of histoplasmosis for a proper detection of either classical or African histoplasmosis coexisting in many sub-Saharan African countries; and the non-availability and accessibility of appropriate antifungal medications were the most challenges in caring DH in advanced HIV disease population in sub-Saharan Africa. Conclusion: there is a need for prompt and routine screening of advanced HIV disease patients in sub-Saharan Africa for histoplasmosis as an AIDS-defining illness.

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Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV—A Case Report from Argentina and Literature Review

Journal of Fungi ◽

10.3390/jof6040275 ◽

2020 ◽

Vol 6 (4) ◽

pp. 275

Author(s):

Fernando A. Messina ◽

Emmanuel Marin ◽

Diego H. Caceres ◽

Mercedes Romero ◽

Roxana Depardo ◽

...

Keyword(s):

Literature Review ◽

Patient Care ◽

Fungal Pathogens ◽

Buenos Aires ◽

Hiv Disease ◽

Rapid Diagnostics ◽

Disseminated Histoplasmosis ◽

Appropriate Treatment ◽

The World ◽

Advanced Hiv Disease

The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.

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The Population Impact of Late Presentation With Advanced HIV Disease and Delayed Antiretroviral Therapy in Adults Receiving HIV Care in Latin America

American Journal of Epidemiology ◽

10.1093/aje/kwz252 ◽

2019 ◽

Vol 189 (6) ◽

pp. 564-572 ◽

Cited By ~ 2

Author(s):

Pablo F Belaunzarán-Zamudio ◽

Yanink N Caro-Vega ◽

Bryan E Shepherd ◽

Peter F Rebeiro ◽

Brenda E Crabtree-Ramírez ◽

...

Keyword(s):

Latin America ◽

Antiretroviral Therapy ◽

Population Attributable Fraction ◽

Immune Deficiency Syndrome ◽

Late Presentation ◽

Hiv Care ◽

Hiv Disease ◽

Art Initiation ◽

Advanced Hiv Disease ◽

The Impact

Abstract Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these conditions on mortality in the region. We included adults enrolled during 2001–2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4 of <200 cells/μL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.

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A Simple Predictive Score to Distinguish between Disseminated Histoplasmosis and Tuberculosis in Patients with HIV

Journal of Fungi ◽

10.3390/jof8010016 ◽

2021 ◽

Vol 8 (1) ◽

pp. 16

Author(s):

Mathieu Nacher ◽

Kinan Drak Alsibai ◽

Loïc Epelboin ◽

Philippe Abboud ◽

Frédégonde About ◽

...

Keyword(s):

French Guiana ◽

Area Under The Curve ◽

Predictive Score ◽

Hiv Disease ◽

Performance Score ◽

Logit Regression ◽

Natural Logarithm ◽

Disseminated Histoplasmosis ◽

Advanced Hiv Disease ◽

Logit Regression Model

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients.

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Antiretroviral Therapy in Advanced HIV Disease: Which is the Best Regimen?

Aids Reviews ◽

10.24875/aidsrev.m17000010 ◽

2018 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Joaquim Burgos ◽

Esteban Ribera ◽

Vicenç Falcó

Keyword(s):

Antiretroviral Therapy ◽

Hiv Disease ◽

Advanced Hiv Disease

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Fiavobacteriurrt spp. organisms as opportunistic bacterial pathogens during advanced HIV disease

Journal of Infection ◽

10.1016/s0163-4453(99)90007-5 ◽

1999 ◽

Vol 39 (2) ◽

pp. 146-152 ◽

Cited By ~ 22

Author(s):

Roberto Manfredi ◽

Anna Nanetti ◽

Morena Ferri ◽

Antonio Mastroianni ◽

Olga V. Coronado ◽

...

Keyword(s):

Bacterial Pathogens ◽

Hiv Disease ◽

Advanced Hiv Disease

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Combination Therapy With Stavudine and Didanosine in Children With Advanced Human Immunodeficiency Virus Infection: Pharmacokinetic Properties, Safety, and Immunologic and Virologic Effects

PEDIATRICS ◽

10.1542/peds.97.6.886 ◽

1996 ◽

Vol 97 (6) ◽

pp. 886-890

Author(s):

Mark W. Kline ◽

Courtney V. Fletcher ◽

Marianne E. Federici ◽

Alice T. Harris ◽

Kim D. Evans ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Combination Therapy ◽

Lymphocyte Count ◽

Hiv Disease ◽

Hiv Rna ◽

Immunodeficiency Virus ◽

Pharmacokinetic Properties ◽

Cd4 Lymphocyte Count ◽

Cd4 Lymphocyte ◽

Advanced Hiv Disease

Objectives. To obtain preliminary information on the pharmacokinetic properties, tolerance, safety, and antiviral activity of combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus (HIV) infection. Methods. Eight children (median age, 6.6 years; range, 2.8 to 12 years) with advanced HIV disease (median CD4+ lymphocyte count at baseline, 42 cells/µL; range, 8 to 553 cells/µL) were treated with stavudine (2 mg/kg per day in two divided doses) and didanosine (180 mg/m2 per day in two divided doses) for 24 weeks. Seven children had histories of prior zidovudine therapy. All children had received stavudine alone for 19 to 33 months before the addition of didanosine to the treatment regimen. Children were assessed clinically and with laboratory studies at baseline, weekly through week 4 of combination therapy, and every 4 weeks thereafter. Results. Analysis of stavudine and didanosine plasma half-life values, clearances, and area under the plasma concentration-versus-time curves revealed no obvious clinical pharmacokinetic interaction between the drugs through study week 12. Combination therapy was well tolerated, and there were no drug-associated clinical or laboratory adverse events. Signs and symptoms of peripheral neuropathy were not observed. All three children with baseline CD4+ lymphocyte counts greater than 50 cells/µL had greater than 20% increases in their counts within the first 12 weeks of therapy; CD4+ lymphocyte count increases were not observed in the other children. Plasma HIV RNA concentrations showed median declines of 0.88 log10 (range, -3.41 log10 to 0.31 log10) and 0.30 log10 (range, -0.63 log10 to 0.89 log10) at study weeks 12 and 24, respectively. Conclusions. Combination therapy with stavudine and didanosine was well tolerated and safe in this small group of children with advanced HIV disease. Plasma HIV RNA concentration declines suggest a favorable effect of therapy on virus load. These findings should be confirmed, and the regimen's clinical efficacy should be examined, in controlled studies of HIV-infected children with less-advanced disease.

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Socio-demographic Determinants of Undernutrition In HIV- Infected Under- Five Children

European Journal of Clinical Medicine ◽

10.24018/clinicmed.2021.2.3.69 ◽

2021 ◽

Vol 2 (3) ◽

pp. 22-29

Author(s):

Sylvia T. Echendu ◽

Ebelechuku F. Ugochukwu ◽

Kenneth N. Okeke ◽

Chinyere U. Onubogu ◽

Joy C. Ebenebe ◽

...

Keyword(s):

Low Socioeconomic Status ◽

Disease Process ◽

Single Parents ◽

Hiv Positive ◽

Growth Monitoring ◽

Hiv Disease ◽

Low Socioeconomic ◽

Under Five ◽

Under Five Children ◽

Advanced Hiv Disease

Background: The disease burden associated with HIV/AIDS is a key factor in the etiopathogenesis of undernutrition in growing children. This is aggravated by resultant social factors in HIV such as orphaning, low socioeconomic status, food insecurity, and marital status of caregivers. Objectives: The relationship between sociodemographic factors and malnutrition in the background of HIV was evaluated. Methods: A cross-sectional descriptive survey was conducted among under-five HIV positive children in Anambra State, Nigeria. Results: A total of 370 HIV positive under-five children comprising 208(56.2%) males and 162(43.8%) females were recruited. The mean age of the children was 44.5±12.9 months. One hundred and forty-seven (39.7%) were globally undernourished: 15.7.0% (58) underweight (WFA <-2SD), 13.3% (49) wasted (WFH < -2SD), and 27.9% (103) stunted (HFA <-2SD). Males were significantly more stunted than females (p<0.001). 77% (285) were of low socioeconomic class (SEC), 47.3% (175) had advanced HIV disease, and 68.1% (252) had been on HAART for >12 months. 26% (96) were orphans, while 28.6% (106) were cared for by single parents. Being on HAART for >12 months was associated with less undernutrition, while advanced HIV disease seemed to enhance it. Children of low SEC were more likely to be undernourished. Not having been breastfed, introduction of complementary feeds at age 3mo or less, poor food variety and suboptimal feeding frequency increased susceptibility to undernutrition. Orphans were more wasted and stunted than underweight. Single parenthood predisposed to undernutrition. Conclusions: HIV-infected children are vulnerable to malnutrition by virtue of the disease process, further compounded by interwoven social dilemma associated with HIV. It, therefore, behooves the health care provider to ensure a proactive growth monitoring and nutritional support, with prompt treatment of co-morbid debilitating infections. There is also a dire need for public health interventions targeted at single parents of low socioeconomic means.

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