The Nairobi Declaration 2023: A commitment to address deadly yet neglected fungal diseases in Africa.

On May 30th and 31st, 2023, delegates representing various African subregions, together with global representatives from the International Society of Human and Animal Mycology (ISHAM), the European Confederation of Medical Mycology (ECMM), the United States Centre for Disease Control and Prevention (CDC), and Global Action for Fungal Infections (GAFFI), convened in Nairobi, Kenya under the aegis of the Pan African Mycology Working Group, a working group of ISHAM. The meeting objectives were, amongst others, to deliberate on a continental response to the World Health Organisation Fungal Priority Pathogen List and facilitate interaction between global and regional leaders. Country delegates and international speakers addressed Africa's fungal disease burden; capacity for diagnosis and management; ongoing surveillance; knowledge gaps and trends in invasive fungal diseases such as Candida auris, mucormycosis, aspergillosis, and Acquired Immune Deficiency Syndrome (AIDS)-related mycoses; and current laboratory practice. During the technical sessions, expert panels deliberated on establishing and financing of national/regional surveillance networks for mycoses; establishing and sustaining African-led collaborations; expanding on existing laboratory and point-of-care diagnostic capacity as well as planning a mycology reference laboratory service and network in Africa. The meeting also highlighted successful African-led collaborations, capacity building, and clinical trial initiatives. The meeting conclusions informed the resolutions of the Nairobi Declaration calling for improved awareness; strong collaborations between clinical and laboratory teams across Africa; improved fungal disease surveillance within the continent; access to antifungals and diagnostics; and leveraging qualified human resources for mycology present within and outside Africa to facilitate trainings, collaborations, and exchanges.

This review presents the current state of the art in medical mycology in Africa discussed at the first scientific meeting of the Pan African Mycology Working Group, an affiliate of the International Society for Human and Animal Mycology (ISHAM) held in Nairobi, Kenya on May 30th and 31st, 2023.

Presence of Burkholderia pseudomallei in Soil, Nigeria, 2019.

Melioidosis, caused by the soil-dwelling bacterium Burkholderia pseudomallei, is predicted to be endemic in Nigeria but is only occasionally reported. This report documents the systematic identification of the presence of B. pseudomallei and B. thailandensis in the soil across multiple states in Nigeria.

Mucormycosis in Africa: Epidemiology, diagnosis and treatment outcomes.

Mucorales fungi cause mucormycosis, an invasive and rapidly progressive disease which increasingly affects mostly immunocompromised but also immunocompetent individuals. The objective of this study was to highlight the epidemiology, diagnostic modalities, treatment and overall survival of mucormycosis in Africa. We searched for relevant publications in PubMed, Google Scholar and African Journal Online databases covering the period 1960-2022. A total of 147 articles were identified, of which 66 were included in the review, detailing 408 individual cases from 12 African countries; 330 (80.9%) from North Africa, 63 (15.4%) from Southern Africa, seven (1.7%) from East Africa, seven (1.7%) from West Africa and a single case (0.2%) from Central Africa. The most frequently described clinical forms were rhino-orbital-cerebral (n = 307, 75.2%) and gastrointestinal (n = 51, 12.5%). Diabetes mellitus, COVID-19, malignancies and neutropaenia were the commonest underlying risks in 203 (49.8%), 101 (24.8%), 65 (15.9%) and 53 (13.0%) cases respectively. Most cases, 296 (72.5%) were diagnosed by histopathology. Fungal aetiology was identified in 38 (9.3%), of which the commonest was Rhizopus oryzae/arrhizus (27/38, 71.1%). Of the 408 cases, 334 (81.9%) patients received antifungal therapy, while 244 (59.8%) had surgery. In cases with a specified outcome, survival rate was 59.1% (228/386). Based on case reporting, a substantial burden of mucormycosis occurs in North Africa but the disease is rarely reported in most of the sub-Saharan region. Establishing a comprehensive registry for standardised data collection could improve understanding of the epidemiology of mucormycosis in the region.

Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria.

We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts <200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had >2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.

Improving awareness, diagnosis and management of invasive fungal infections in Ghana: establishment of the Ghana Medical Mycology Society.

Invasive fungal infections (IFIs) and medical mycology receive little attention in Ghana. However, the present evolution of biomarker assays for IFIs, offers an opportunity for an increased access to fungal laboratory testing in resource-limited settings, and probably make a case for availability of essential antifungal agents. Using surveys and personal communications, the state of medical mycology and IFI in Ghana were highlighted. Inadequate awareness and insufficient access to fungal diagnostics and therapeutics were identified as the key challenges, the establishment of the Ghana Medical Mycology Society was discussed, and recommendations were made to improve the status quo.

Invasive fungal infections (IFIs) receive little attention in Ghana, despite its growing relevance globally. Using surveys and personal communications, the main challenges were identified, and the formation of the Ghana Medical Mycology Society was discussed as a tool to improve the status quo.

Bridging the knowledge gap on mycoses in Africa: Setting up a Pan-African Mycology Working Group.

Most African countries have poorly funded and overburdened health systems. Additionally, a high prevalence of HIV in Sub-Saharan Africa contributes to a high burden of opportunistic fungal infections. Data generated by GAFFI from 15 of 57 African countries revealed that an estimated 47 million Africans suffer from fungal diseases, of whom an estimated 1.7 million suffer from a serious fungal infection annually. Almost all African countries lack a surveillance system for fungal infections with the exception of South Africa. South Africa is also the only African country with a national mycology reference laboratory. Across the continent, there is a pervasive picture of inadequate/poor diagnostic capacity, low level of awareness among healthcare workers and policymakers and unavailability and non-accessibility to essential antifungal medications. Recent outreach efforts by the International Society for Human and Animal Mycology (ISHAM) and the European Confederation of Medical Mycology (ECMM) have aimed to increase involvement of African countries and experts in global initiatives such as "One World One Guideline" and also the ECMM Academy. Recently, under the auspices of ISHAM, the African sub-region created a network of mycology experts whose goal is to organise and engage African leaders in the field of medical mycology. The aim of this ISHAM Working Group was to facilitate interaction and synergy among regional leaders in order to develop educational programmes for capacity building to aid in the diagnosis and care of patients with fungal infections in Africa. The working group will also encourage country initiatives to develop clinical guidelines, to support surveys and to support the establishment of reference mycology laboratories.

The role of medical mycology societies in combating invasive fungal infections in low- and middle-income countries: A Nigerian model.

The discipline of medical mycology has become increasingly relevant in the face of the rising incidence of invasive fungal infections (IFI), which pose diagnostic and therapeutic challenges for contemporary medical practice. While firmly established in developed countries, medical mycology remains obscure in many low- and middle-income countries (LMICs). With a teeming vulnerable populace and an incidence rate of 11.8%, Nigeria has one of the highest estimated burdens of invasive fungal infections (IFIs) in the world. Regardless, the scourge of IFIs has remained silent due to a combination of factors principal amongst which are a lack of awareness and dearth in personnel skilled in diagnosis. The present narrative examines the status of medical mycology practice in Nigeria and chronicles the journey to change the status quo spurred by the Leading International Fungal Education (LIFE)-facilitated burden estimate paper and culminating in the birth of the Medical Mycology Society of Nigeria (MMSN), the pioneer national medical mycology society in Africa. The prospects of tackling the IFI challenge are highlighted from the perspective of the nascent society.

Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species.

Fluconazole is the most commonly used antifungal agent for both the treatment of cryptococcal meningitis, and for prophylaxis against the disease. However, its prolonged use has the potential to exert selection pressure in favour of fluconazole-resistant strains. We evaluated the prevalence of fluconazole resistance in Cryptococcus spp. clinical isolates in 29 studies from 1988 to May 2017 included in EMBASE and MEDLINE databases. A total of 4995 Cryptococcus isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates from relapsed episodes of cryptococcosis were included in this analysis. Eleven (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of ≥64 µg/mL to define fluconazole resistance, 6 (21%) used ≥32 µg/mL, 11 (38%) used ≥16 µg/mL and 1 (3%) used ≤20 µg/mL. Overall, mean prevalence of fluconazole resistance was 12.1% (95% confidence interval [CI]: 6.7-17.6) for all isolates (n = 4995). Mean fluconazole resistance was 10.6% (95% CI: 5.5-15.6) for the incident isolates (n = 4747) and 24.1% (95% CI: -3.1-51.2) for the relapse isolates (n = 248). Of the 4995 isolates, 936 (18.7%) had MICs above the ecological cut-off value. Fluconazole resistance appears to be an issue in Cryptococcus isolates from patients with relapses. It remains unclear whether relapses occur due to resistance or other factors. There is an urgent need to establish antifungal breakpoints for Cryptococcus spp.

Fungal contamination of the water distribution system of a tertiary hospital water supply system in a resource-limited setting.

Background: Fungal contamination of hospital water distribution systems has been implicated in outbreaks of healthcare-associated infections. Objectives: To evaluate the prevalence of fungi in the water distribution system of a tertiary hospital in Nigeria. Design: This was a descriptive cross-sectional study. Methods: Swabs and water samples were collected from taps and faucets in the hospital categorized into low (Accidents and Emergency Unit, Children Emergency Unit, Acute Stroke Unit and the 24 in-patient hospital wards) and high-risk (Renal Dialysis Unit, Central Sterile Services Department, Theatres and Intensive Care Units (ICUs)) units based on the vulnerability of patients being managed there. The membrane filtration method for water analysis was used. Where possible, isolates cultured were identified to species level. In total, 105 water and 49 swab samples were collected for analysis. Results: All analysed water samples grew fungi. A total of 289 (high-risk; n = 178; low-risk; n = 111) and 76 fungi isolates were recorded from water and swab samples, respectively, with 31 different species identified. Aspergillus was the most predominant genus with five different species: Aspergillus niger (9.9%), terreus (4.4%), flavus (3.3%), fumigatus (8.8%) and versicolor (2.20%) isolated. Twenty-five and 18 species of fungi were identified in the low and high-risk units, respectively. The labour ward (n = 46; 25.8%) and modular theatre (n = 47; 42.3%) were the most contaminated units. Cladosporium spp. and Paecilomyces spp. were the most frequently isolated fungi in the low and high-risk units, respectively. The dialysis centre (n = 9; 8.1%) and renal transplant theatre (n = 7; 6.31%) had the lowest contamination rates in the high-risk units. Aspergillus niger, Cephalosporium curtipes, Penicillium chrysogenum and Penicillium glabrum were each identified in 4/6 units from which swabs were taken. The facility had no documented protocol for its water safety and quality. Conclusion: Our data reveal a high rate of contamination of hospital water sources by fungi, some of which are known to cause life-threatening infections. For better water treatment and water tank cleaning and disinfection, a standard protocol is advised. Ensuring that the water distribution systems in hospital settings are free of fungal contaminants is important to prevent the possibility of waterborne mycosis outbreaks.

Candida auris: A Systematic Review of a Globally Emerging Fungal Pathogen in Africa.

Candida auris is a World Health Organization critical priority fungal pathogen. We conducted a systematic review to describe its epidemiology in Africa. PubMed and Google scholar databases were searched between January 2009 and September 2023 for clinical studies on C. auris cases and/or isolates from Africa. Reviews were excluded. We included 19 studies, involving at least 2529 cases from 6 African countries with the most, 2372 (93.8%), reported from South Africa. Whole-genome sequencing of 127 isolates identified 100 (78.7%) as clade III. Among 527 isolates, 481 (91.3%) were resistant to fluconazole, 108 (20.5%) to amphotericin B, and 9 (1.7%) to micafungin. Ninety of 211 (42.7%) patients with clinical outcomes died. C. auris is associated with high mortality and antifungal resistance, yet this critical pathogen remains underreported in Africa. Collaborative surveillance, fungal diagnostics, antifungals, and sustainable infection control practices are urgently needed for containment.

Prevalence of Chronic Pulmonary Aspergillosis in Two (2) Tuberculosis Treatment Clinics in Lagos, Nigeria: A Prospective Longitudinal Study.

Background: Chronic pulmonary aspergillosis (CPA) is an underrecognized but common complication of pulmonary tuberculosis. In Nigeria, a tuberculosis-endemic country, there is currently no provision to monitor the development of CPA in patients treated for tuberculosis. This study determined the prevalence and incidence of CPA in Lagos, Nigeria. Methods: A prospective longitudinal study of patients with previously managed tuberculosis was conducted between June 2021 and May 2022. The study cohorts were assessed at 3-month intervals, and the following were collected: sociodemographic data, chest radiographic findings, sputum samples for fungal culture, and venous blood samples for Aspergillus immunoglobulin G estimation. CPA cases were determined using the case definition for resource-constrained countries. Descriptive and inferential statistics were used, and significance was set at a probability of 5% (P < .05). Results: Of the 141 patients recruited, 79 (56.0%) were in the retreatment and 62 (44.0%) in the posttreatment tuberculosis group. The median age (interquartile range) was 40 (30-52) years, with a male-to-female ratio of 1.1:1. Ninety-seven patients (69%) had a GeneXpert test done, of whom 63 (64.9%) were GeneXpert negative. Cough was the most common symptom, with 15 (11%) patients having hemoptysis. The rate of CPA increased steadily as the study progressed: 44 (31.2%) at commencement, 45 (34.9%) at 3 months, 49 (42.6%) at 6 months, and 51 (54.3%) at 9 months. Thus, the overall prevalence of CPA was 49.7%, and the incidence was 6.1%. Conclusions: CPA is common in Nigeria and its true burden may still be underestimated. Increased awareness of CPA as a posttuberculosis lung disease is advocated. Evaluation for CPA should be incorporated in patients' work-up for tuberculosis.

Universal use of face mask for the prevention of the spread of COVID-19 in community settings in a South-western State of Nigeria: willingness and barriers.

BACKGROUND AND OBJECTIVES: One of the major drivers of the novel coronavirus (SARS-CoV-2) pandemic is community transmission. Nigeria, like other countries globally, took to strict preventive public health measures including good respiratory and hand hygiene, physical distancing, and the use of face mask to control the spread of COVID-19 disease. Furthermore, the government of Lagos State in Nigeria made a pronouncement on the universal use of face mask in the community. While the use of face masks has proven to be an effective barrier to the transmission of respiratory diseases, its use in the community is uncommon. This study assessed the willingness and compliance with wearing face masks for the reduction of the community spread of COVID-19 and identified possible barriers to use of mask among residents in Lagos State. METHODS: This was a descriptive cross-sectional study, that surveyed 552 respondents who were adult residents of Lagos State. Data collection was quantitative, using a pretested, interviewer-administered questionnaire, and findings were presented in frequencies and percentages. Pearson's chi-square and logistic regression analyses were used to test the association between variables. The level of significance was set at 5%. RESULTS: A majority (75.7%) of the respondents were willing to wear a face mask in public areas but only 21.9% of the respondents were willing to wear a mask at all times. The most identified barriers to wearing mask were discomfort (72.5%) and inconvenience (77.7%). Two-thirds of the respondents reported they were compliant with always wearing a face mask when leaving home. Only 15.0% of the respondents wore the mask continuously and appropriately, covering the nose and mouth. Having a post-secondary education and being older (40 years and above) were found to be positive predictors of both willingness to wear a mask and compliance with universal mask policy (wearing masks continuously and appropriately). CONCLUSION: Our findings suggest that willingness to wear a face mask influences compliance, and that having a post-secondary education and being older (> 40 years) were positive predictors of both willingness to wear a mask and compliance with universal mask policy (wearing it continuously and correctly). The major barriers to wearing masks were discomfort and inconvenience. Effective risk communication strategies to reach diverse groups for better compliance with public health measures are urgently needed even for the future.

Gastrointestinal Histoplasmosis: A Descriptive Review, 2001-2021.

Gastrointestinal histoplasmosis (GIH) is infrequently described in people without underlying HIV infection. We aimed to compare the clinical presentation of GIH in people with and without HIV infection. We conducted a literature search of published cases of GIH from 2001-2021 and found 212 cases. Of these, 142 (67.0%) were male, and 124 (58.5%) had HIV infection. Most cases were from North America (n = 88, 41.5%) and South America (n = 79, 37.3%). Of the 212 cases, 123 (58.0%) were included in both clinical and pathological analyses. The remainder were excluded as details about clinical and pathological findings were not available. Of the 123 cases, 41 had HIV infection while 82 were without HIV infection. The diagnosis was predominantly by histopathology (n = 109, 88.6%). A significant proportion of people with HIV infection had abdominal pain as the most predominant symptom of GIH compared to those without HIV infection (65.9% versus 41.9%, p < 0.05). The colon was the most affected site with a slightly higher proportion in those with HIV infection compared with cases without HIV infection (46.3% versus 42.7%). The commonest pathologic findings were caecal and ileal ulcers. Caecal ulcers were significantly more frequent in cases with HIV infection compared to those without HIV (32.1% versus 7.1%, p < 0.05). Despite being more common in people with HIV infection, GIH also affects people without HIV infection with similar clinical presentations.

Rapid Diagnostic Test Value and Implementation in Antimicrobial Stewardship Across Low-to-Middle and High-Income Countries: A Mixed-Methods Review.

Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

A multicenter survey of asymptomatic cryptococcal antigenemia among patients with advanced HIV disease in Nigeria.

As of 2018, cryptococcal antigen (CrAg) screening in patients with advanced human immunodeficiency virus (HIV) disease (AHD) was not routinely implemented in Nigeria despite being recommended in the national HIV treatment guidelines. Our aim was to determine the prevalence and risk factors for asymptomatic cryptococcal antigenemia in adult people living with HIV (PLHIV) in Nigeria to advocate for the implementation of routine CrAg screening. A descriptive cross-sectional study and CrAg screening of consecutive adult PLHIV with CD4 counts ≤200 cells/µL was conducted from April 2018 to April 2019 at HIV clinics in eleven tertiary hospitals spread across Nigeria's six geopolitical regions. Prevalence of asymptomatic cryptococcal antigenemia was estimated by facility and geopolitical zone. Logistic regression was conducted to identify risk factors for cryptococcal antigenemia. In total, 1,114 patients with AHD were screened. The overall prevalence of asymptomatic cryptococcal antigenemia was 3.9% with wide variation across facilities (range: 0/75 [0%]- 15/122 [12.3%]) and geopolitical zones (range: 0/75 [0%]-19/279 [6.8%]). Prevalence of antigenemia was highest in the South-West (19/279 [6.8%]) and lowest in the North-East (0/75 [0%]). Prevalence was 5.2% (26/512) and 3.2% (18/561) in patients with CD4<100 and CD4 of 101-200, respectively. Of all patients with antigenemia, 50% were on antiretroviral therapy (ART) at the time of having a positive CrAg test. In adjusted analysis, cryptococcal antigenemia was significantly less in patients on ART and patients who had completed any formal education. The survey showed a high overall burden of cryptococcal antigenemia in Nigeria, with variable prevalence across geopolitical regions. We provided valuable evidence for implementing routine CrAg screening of AHD patients in Nigeria which has commenced in selected centres.

Our pursuit for effective antifungal agents targeting fungal cell wall components: where are we?

Invasive mycotic infections present unacceptably high mortality rates in humans. These infections are initiated by the fungal cell wall, which mediates host-fungi interactions. The cell wall is associated with the physiology of fungi and is involved in essential processes in the entire cell functionality. Components of the fungal cell wall are synthesised and modified in the cell wall space by the activities of cell wall proteins through a range of signalling pathways that have been described uniquely in many fungi, therefore making them suitable drug targets. The echinocandin class of cell-wall-active drugs blocks cell wall ß-1,3-glucan biosynthesis through inhibiting the catalytic subunit of the synthetic protein complex. Resistance to echinocandins can occur through the acquisition of single nucleotide polymorphisms and/or through activation of cell wall signalling pathways resulting in an altered cell wall proteome and elevated chitin content in the cell wall. Countering the cell wall remodelling process will enhance the effectiveness of ß-1,3-glucan-active antifungal agents. Cell surface proteins are also important antifungal targets that can be used to develop rapid and robust diagnostics and more effective therapeutics. The cell wall remains a crucial target in fungi that needs to be harnessed to combat mycotic infections.

Histoplasmosis in African children: clinical features, diagnosis and treatment.

Most of the reviews on histoplasmosis documented in literature have been in the adult population. Very few studies highlight the peculiarities associated with histoplasmosis in Africa especially in the pediatric population. This review addresses the above concerns with clinical summaries and diagnosis of some case reports of histoplasmosis in African children. We highlighted 44 case reports of histoplasmosis in African children (1950-2021) distributed across Western Africa (38.6%, n = 17), Eastern Africa (9.1%, n = 4), Southern Africa (9.1%, n = 4), and Central Africa (43.2%, n = 19). No case report was found from Northern Africa. The age range was 1-17 years, with a mean of 9.2. Of the 44 case reports, 8 cases (18.2%, 8/44) were caused by Histoplasma capsulatum var capsulatum, 33 cases (75%, 33/44) were caused by Histoplasma capsulatum var duboisii, and specie identification was not found in 3 cases. Only three (6.8%) cases were HIV positive; 56.8% (25/44) were disseminated histoplasmosis, pulmonary histoplasmosis accounted for just one case (2.3%, 1/44). Extrapulmonary presentation included skin lesions (ulcers, fistulas, nodules, patches, pigmentations, papules, and abscesses), bone lesions, osteoarthritis, and fractures. The commonest sites affected were skin (n = 29, 65.9%), bones (n = 20, 45.5%), and lymph nodes (n = 15, 34.1%). Histopathology was the commonest diagnostic method (n = 33, 75%). Amphotericin B was first-line therapy in 45.5% of the cases (n = 20) followed by ketoconazole (20.5%, n = 9); 27 cases (61.4%) had favorable outcomes, 8 cases (18.2%) had fatal outcomes, while in 9 cases, the outcome was not revealed. This review revealed several cases of histoplasmosis misdiagnosed as other conditions including tuberculosis (n = 3, 6.8%), pneumonia (n = 1, 2.3%), cancers (n = 4, 9.1%), nephritic syndrome (n = 1, 2.3%), leishmaniasis (n = 1, 2.3%), and hyperreactive malarial splenomegaly syndrome (n = 1, 2.3%). In addition, histoplasmosis was not considered in some case reports even when symptoms were suggestive. Diagnosis of histoplasmosis was made at autopsy with postmortem findings suggestive of histoplasmosis (n = 3, 6.8%). This report highlights the need for a paradigm shift on the part of pediatricians in Africa. They need to look beyond clinical conditions considered common in our environment for this age group and evaluate for other diseases including histoplasmosis.

Prevalence of Histoplasmosis and Molecular Characterization of Histoplasma species in Patients with Presumptive Pulmonary Tuberculosis in Calabar, Nigeria.

Background: Several case reports abound in literature about cases of histoplasmosis misdiagnosed as tuberculosis (TB). Nigeria is one of the highest TB-burdened countries, but data on histoplasmosis in Nigeria are sparse in the literature. The aim of this research was to investigate patients with presumptive pulmonary TB in Calabar, Nigeria, for histoplasmosis. Methods: This was a descriptive cross-sectional study of 213 participants with presumptive diagnosis of pulmonary TB between April 2020 and March 2021. Urine samples were collected from selected patients for Histoplasma antigen test using enzyme immunoassay kits, while sputum samples were collected for GeneXpert test for confirmed diagnosis of TB and conventional polymerase chain reaction (PCR) for the diagnosis of histoplasmosis. Results: Of the 213 participants enrolled into the study, 94 subjects (44.1%) were confirmed TB patients, 75 (35.2%) were human immunodeficiency virus (HIV) positive, 41 (19.2%) had advanced HIV disease (AHD), and 138 (64.8%) were HIV negative. Twenty-seven of the 213 participants were Histoplasma positive by antigen test and/or PCR, giving an overall prevalence rate of 12.7%. The prevalence of histoplasmosis among confirmed TB patients (7.4% [7/94]) was significantly lower than in unconfirmed TB patients (16.8% [20/119]) (P = .04). Participants on anti-TB therapy also had a significantly lower rate of histoplasmosis compared to those not on anti-TB drugs (P = .00006). The internal transcribed spacer (ITS) sequencing of the Histoplasma revealed a closely relatedness to Histoplasma capsulatum. Conclusions: Histoplasmosis is not uncommon among presumptive TB patients. There should be proper microbiological investigation of patients presenting with symptoms suggestive of TB to exclude cases of histoplasmosis.