THE NAIROBI DECLARATION 2023: A COMMITMENT TO ADDRESS DEADLY YET NEGLECTED FUNGAL DISEASES IN AFRICA

Abstract

On May 30^th and 31^st, 2023, delegates representing various African subregions, together with global representatives from the International Society of Human and Animal Mycology (ISHAM), European Confederation of Medical Mycology (ECMM,) 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 Organization 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.

Lay summary

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.

Introduction

The Pan African Mycology Working Group (PAMWG) is a network of medical mycology experts set up under the auspices of the International Society for Human and Animal Mycology (ISHAM) during an international conference hosted by the Medical Mycology Society of Nigeria in Lagos in 2018.¹ The group provides a platform for leaders in the field of medical mycology from multiple African countries to initiate epidemiological studies, develop regional guidelines, and educational programs to increase the capacity of African health care personnel (HCP) to quickly detect and treat serious fungal infections. Amongst other activities, the organisation of local meetings in collaboration with ISHAM is pivotal to the realisation of the group’s objectives. Due to the coronavirus 2019 (COVID-19) pandemic, initial plans to organise an inaugural meeting were deferred to 2023. The release of a Fungal Priority Pathogens list (FPPL) by the World Health Organization (WHO) in October 2022,² besides communicating a global commitment to tackling the under-recognised and underfunded burden of invasive fungal diseases (IFDs), also sounded a call to action which stimulated the leadership of the PAMWG to re-ignite plans for the 1^st PAMWG meeting.

The meeting was a two-day conference convened in Nairobi, Kenya from May 30^th to 31^st, 2023 with opportunity for virtual participation. Delegates from Cameroon, Egypt, Ghana, Ivory Coast, Kenya, Morocco, Nigeria, Senegal, Sudan, South Africa, Tanzania and Uganda, converged for what was unanimously perceived as an epoch-defining moment for medical mycology in the continent. Also present were delegates from the International Society for Human and Animal Mycology (ISHAM), European Confederation of Medical Mycology (ECMM), United States Centers for Disease Control and Prevention (CDC) and Global Action for Fungal Infections (GAFFI).

The specific objectives of this conference were

1. To raise awareness of serious fungal diseases and start the discussion on a continental response to the recently published WHO FPPL which focuses on strengthening laboratory capacity and surveillance; sustainable investments in research, development and innovation and public health interventions

2. To facilitate interaction and synergy among global and regional leaders to develop educational programs for capacity building to aid in the diagnosis and management of fungal infections in Africa.

3. To address knowledge gaps about fungal diseases in Africa

4. To improve access to antifungal agents and diagnostic tests for the major fungal diseases in the different African countries

5. To address the challenges regarding diagnosis and management of fungal diseases through technical sessions, proffer solutions, set up collaborations and develop a consensus document on the meeting resolutions.

This report summarises recent developments concerning epidemiology, diagnosis and management of invasive fungal diseases in Africa as well as the persisting gaps, challenges and future prospects as posited by expert delegates at the first PAMWG conference.

Burden of serious fungal diseases in Africa, capacity for diagnosis and treatment

While there is a growing burden of life-threatening fungal diseases globally, low- and middle-income countries are disproportionately affected because of late presentations, misdiagnoses occasioned by limited diagnostic tools and low index of suspicion; sub-optimal therapy arising from poor antifungal access and affordability as well as low capacity for therapeutic drug monitoring. Prolonged hospitalisations and exorbitant costs due to lack of health insurance complicate matters, often resulting in poor outcomes. In contrast with high income countries where advanced and novel treatments place patients at risk of invasive fungal diseases, the major drivers in Africa are poverty, tuberculosis and human immunodeficiency virus (HIV). Additional contributing factors include chronic obstructive pulmonary disease, asthma, diabetes mellitus, the increasing use of intensive care, haemato-oncological conditions and COVID-19.³ The true burden of IFDs in Africa remains unknown because surveillance data are limited, and clinical studies are few. Nevertheless, there have been efforts by GAFFI to generate credible burden estimates in at least 18 African countries and South Africa boasts of robust surveillance data for some fungal diseases. Secondary data sources include modelling studies and systematic reviews.⁴ Cryptococcosis, which is the most common and most studied mycosis in Africa, is estimated to affect over 152,000 adults with advanced HIV disease annually and contribute to 19% of AIDs-related deaths.⁵ Diagnosis has been made simpler with the use of a highly-accurate point of care test which is available in many countries and treatment guidelines for HIV-associated cryptococcosis exist. However, management challenges persist since flucytosine and liposomal amphotericin B, cornerstone antifungals, remain expensive and not widely available. More extensive gaps exist in the knowledge of epidemiology, diagnosis and treatment for other mycoses. Recommendations made to bridge these gaps are listed in Table 1.

Table 1:

Proposed strategies to bridge gaps in understanding the burden of mycoses in Africa

Recommendation	Modus operandi
Popularising the WHO FPPL through various media channels	Highlights fungi of critical or high importance to human health, providing pathways for action such as engagement with policy makers
Providing diagnostics and setting up surveillance systems	Provides data on disease burden and antifungal susceptibility patterns.
Implementation science research in medical mycology	Improves uptake of diagnostics and public-health interventions targeting IFDs, thereby improving case-finding.
Investing in and increasing pre-service and in-service trainings for HCP of all categories	Makes HCP knowledgeable to promptly detect IFDs

WHO= World Health Organisation; FPPL= Fungal Priority Pathogens List; HCP= Healthcare personnel; IFD= Invasive fungal disease

Laboratory diagnostic capacity and access to antifungal treatment are pivotal to the effective management of IFDs. Assessing the regional status of these crucial variables is necessary to guide health professionals, patients, and policy makers.⁶ ECMM/ISHAM have conducted recent surveys providing information on diagnostic and therapeutic capacity for the management of IFDs in Europe, Asia/Pacific and African regions.^6–8 These surveys were web-based and included 388 institutions from 45 countries in Europe; 235 institutions from 40 countries in Asia/Pacific; but only 40 institutions from 21 countries translating to a response rate below 25% in Africa. The low numbers of responders from Africa might reflect the fact that there are few mycologists on the continent.⁸ However, the limited survey responses revealed low access to susceptibility testing for both yeasts and moulds and Aspergillus antigen detection. Apart from fluconazole which was available in 90% of African institutions, access to other antifungals (also designated WHO essential medicines) such as amphotericin B deoxycholate (available for 52·5% of institutions), liposomal amphotericin B (17.5%) and the mould-active triazoles, itraconazole (52·5%), voriconazole (35·0%) and posaconazole (5·0%) was also low. While more detailed and robust analysis still need to be undertaken to understand the true extent of challenges faced, the current results are sufficient to advocate for better diagnostic and therapeutic resources for IFDs in Africa.⁸

Trending invasive fungal diseases in Africa

Candida auris

Candida auris, which is classified as a critical pathogen on the WHO FPPL, was first reported in 2009 and has now been documented in six African countries, namely; South Africa, Kenya, Nigeria, Sudan, Egypt and Algeria.^9–13 Due to the need for largely unavailable, sophisticated laboratory tests (matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) and/or ribosomal DNA (rDNA) sequencing of internal transcribed spacer (ITS)/D1-D2 regions), the yeast is often misidentified in laboratories, a possible reason for the paucity of data from the continent. Most reported cases appear sporadic; however, confirmed outbreaks have been described in South Africa and Kenya. In South Africa where the most cases have been recorded, C. auris is a leading cause of candidaemia especially in private sector hospitals in Johannesburg, Gauteng province, South Africa and protracted outbreaks have been reported from neonatal intensive care units within the country.⁹ In 2019, 11 invasive cases of C. auris were identified in the intensive care and high-dependency units of a hospital in Nairobi, Kenya.¹⁰ Multimodal interventions were instituted including intensified infection prevention and control (IPC) measures, point prevalence surveys to monitor on-going transmissions, admission and contact screening to promptly detect colonized patients. Delegates from both South Africa and Kenya highlighted resource challenges in implementing C. auris screening and instituting IPC measures for outbreak control.

Mucormycosis

In contrast to C. auris, mucormycosis was first described in humans in the 1800s. It is caused by mucoraceous fungi which are ubiquitous in nature and distributed globally. There remains a paucity of data about mucormycosis in Africa. A recent review of published case reports and series analysed 408 documented cases, most of which were reported from North Africa, predominantly Egypt.¹⁴ Fewer than 10 cases were reported from each of the East, West and Central African regions. The review also noted that only 38 isolates were cultured suggesting a lack of laboratory capacity. Most cases were treated with amphotericin B deoxycholate while only few received globally recommended antifungals such as liposomal amphotericin B and posaconazole and some were managed with inappropriate therapies such as ketoconazole and fluconazole. While mucormycosis appears rare, an upsurge in cases was demonstrated during the COVID-19 pandemic and anecdotal evidence provided during the conference also suggests that the disease may be underreported in scientific literature. Knowledge and practice gaps noted include the true prevalence of mucormycosis especially for clinical phenotypes besides rhino-orbitocerebral, the species of mucoraceous fungi causing mucormycosis in Africa, and the ways to access effective antifungal agents, such as posaconazole and liposomal amphotericin B, at reasonable costs. Recommendations to bridge these gaps include knowledge, practice and perception studies; research and development to develop rapid, point of care tests; operating a disease registry and leveraging drug access programmes for other diseases, such as HIV-related cryptococcal meningitis, for liposomal amphotericin B.

Aspergillosis

Aspergillosis is a spectrum of diseases caused by Aspergillus species. It mostly affects the lungs and ranges from allergic to chronic and invasive forms. Despite the presence of risk factors such as advanced HIV, escalating cancer burdens, and critical illnesses such as COVID-19, invasive aspergillosis is rarely diagnosed in Africa. In their systematic review, Yerbanga et al dispelled the notion of IA in Africa as a myth.¹⁵ This review identified case reports and observational studies documenting IA in African countries. The prevalence of IA approached 27% in haemato-oncology patients with a fatality rate of more than 60% recorded. Invasive pulmonary aspergillosis was the most common clinical form of IA while neutropenia, HIV/AIDS and renal transplant were the main predisposing conditions. Aspergillus flavus and A. niger were the main species identified and A. fumigatus was surprisingly uncommon. This species profile, distinct from developed countries where A. fumigatus causes more than 80% of IA, has been observed in other tropical regions such as the Indian sub-continent, and may be related to climate and geographic factors. Management with antifungals was often started only after broad-spectrum antibiotic therapy failed. Lack of qualified human resources in medical mycology, diagnostic tools, clear diagnostic guidelines and therapeutic drug monitoring were among the barriers to caring for patients with IA.

Unlike the invasive form, chronic pulmonary aspergillosis (CPA) has been recognised as a post-TB lung disease since the 1960s but remained a neglected condition in Africa until recently. Reporting of CPA cases in Africa has risen progressively since the turn of the century, an indication of increasing recognition of its public health importance brought about by awareness creation championed by GAFFI and collaborators.¹⁶ CPA affects patients with structural lung defects. Since pulmonary TB heals with scarring, fibrosis, or cavity formation, it is one of the commonest at-risk conditions for CPA, and is responsible for 1.2 million of the estimated 3 million CPA cases globally.¹⁶ As Africa has several high-TB burden countries, the prevalence of post-TB CPA is expectedly high. Nigeria’s TB burden is ranked as the largest in Africa and sixth largest globally. In 2021, Nigeria accounted for 4.4% of the global number of TB cases, with 590,000 new cases of TB reported, an increase from the 452,000 reported in 2020. In a prospective longitudinal study to determine at what stage post-treatment for TB that patients would develop CPA, the prevalence at recruitment was 31.2% but increased steadily to 31.9%, 34.8% and 36.2% at 3, 6 and 9 months respectively (Davies et al, unpublished data). In a population-based study of previously treated PTB patients in Uganda, another country where TB is endemic and diagnosing CPA presents a dilemma, about 6.5% of the participants developed CPA within 2 years of TB treatment.¹⁷ A more recent study in Uganda revealed that 20% of persons with persistent respiratory symptoms after 2 months of standard anti-TB treatment had CPA.¹⁷ According to data from the National tuberculosis and leprosy programme in Tanzania, only 34% of all new TB cases were bacteriologically confirmed in 2020 and 43% of all cases were clinically diagnosed. Despite recommendations of the WHO for molecular diagnostics as the preferred first-line testing option, only 63% of all notified cases were bacteriologically confirmed using any method. This gap in bacteriologically confirmed TB may very well point to the burden of CPA in Tanzania. Additional research is obviously needed to fully elucidate the burden and impact of CPA, especially post-TB treatment, on individual and public health. A systematic inclusion of CPA monitoring in TB programmes was recommended where persons suspected and confirmed to have TB are investigated for CPA during and after the completion of anti-TB therapy. Challenges encountered in all settings, whether while managing CPA or conducting research studies, include low level of clinicians’ awareness, similarities of clinical signs and symptoms with TB and unavailability of Aspergillus-specific serological diagnostics in most African countries (Aspergillus IgG antibody testing was reported to be regularly done only in Morocco; occasionally done in Tunisia, Niger and Chad; and never done in 39 countries).¹⁸

Aspergillosis is most commonly managed using mould-active azoles including itraconazole and voriconazole. Azole resistance is a globally emerging phenomenon which can severely hamper treatment. It often occurs following treatment but could also arise de novo in environmental isolates of Aspergillus fumigatus which have been exposed to azole containing fungicides used in the agricultural sector. Despite large agrarian communities and poor antimicrobial, including antifungal, stewardship, there is paucity of data on azole resistance in Africa, especially since many laboratories lack the capacity to perform antifungal susceptibility testing. Pooling all available data from Africa in a systematic review, Amona et al estimated an overall prevalence of triazole resistance of 17.1% in environmental isolates and 1.3% in clinical isolates.¹⁹

Overarching recommendations

Overall, there is an urgent need for intensive surveillance in order to better understand the burden of these trending fungal diseases in the continent. Effective surveillance requires considerable resources; thus, African countries need to invest in efficient disease surveillance mechanisms. South Africa possesses the most established fungal disease surveillance system in Africa owing to decades of investment into a national diagnostic laboratory network and integration of a mycology reference laboratory into the country’s national public health institute. This infrastructure is currently being leveraged to facilitate a sub-regional surveillance network. In Nigeria, surveillance is currently being undertaken at sentinel sites under the auspices of Nigerian Fungal Disease Surveillance and Capacity Building (NIFUSCAB) with support from the US CDC and Nigeria Centre for Disease Control (NCDC). These two models show that despite the challenges, surveillance for fungal disease is feasible in Africa.

AIDS and Mycoses

Africa accounts for majority of global deaths from advanced HIV and a substantial number of these deaths are caused by AIDS-related mycoses.²⁰ Two of these fungal killers-histoplasmosis and cryptococcosis- were spotlighted.

Disseminated histoplasmosis in Africa’s advanced HIV disease (AHD) population has remained neglected for more than three decades of the HIV pandemic.²¹ Poor awareness and lack of context-appropriate diagnostic tools present the major challenges to the diagnosis and management of the disease. Greater public health focus on tuberculosis which is endemic in many parts of Africa also confounds the diagnosis of histoplasmosis. Culture of the causative organism, Histoplasma capsulatum is 100% specific and regarded as the gold standard for diagnosis but it is slow, has poor sensitivity and often, facilities for culture are not available.²² For this reason, the Pan American Health Organization and WHO guidelines recommend antigen detection assays for diagnosing disseminated histoplasmosis in persons with HIV. Only recently, a study conducted using antigen detection assays, determined a 7.7% prevalence of disseminated histoplasmosis in Nigeria.²³ These assays, however, are still not readily available in most African countries. In Nigeria, an enzyme immunoassay-based technique has been piloted but challenges have been experienced with respect to required equipment and personnel training. Moreover, requirements for sample batching have resulted in prolonged turnaround times for results, delayed treatment and fatal outcomes in some instances. As a matter of urgency, highly accurate rapid diagnostic tests (RDTs) need to be made accessible, through better government-sponsored health insurance packages, at facilities providing AHD care, as they could be life-saving in the resource-limited context characteristic of African countries.

Unlike histoplasmosis, cryptococcosis is a well-researched and well-documented AIDS-related mycosis with much of the evidence about the disease generated in Africa. Much progress regarding diagnosis and treatment has been made over the years: a simple, efficient diagnostic tool, the IMMY Crag lateral flow assay, has been in use for over a decade and effective treatment regimens have been determined following rigorous clinical trials.²⁴ Nonetheless, translating this evidence into routine practice remains problematic in Africa. Some of the barriers to effective management of CM include deferral of diagnostic and therapeutic lumbar punctures either due to reluctance of local clinicians to perform the procedure or high refusal rates amongst patients, and the pervading lack of access to antifungals like liposomal amphotericin B and flucytosine. The practice gaps in CM care underscore the need for implementation science and research as well as health systems strengthening without which deaths from CM will remain high in the continent. As an example, the Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) implementation science project adapted standard operating procedures from CM clinical trials for use in routine care settings in Africa. This reduced all-cause 2-week mortality from 49% to 24% among people living with HIV presenting to public hospitals in Africa with suspected HIV-related CNS infection.²⁵

Laboratory and point of care tests; current realities and future perspectives

IFDs often present with non-specific symptoms and require laboratory tests for confirmation. At the same time, diagnostic delays are associated with an increased risk of death while early diagnosis and the institution of appropriate antifungal therapy are directly linked to improved survival. The pivotal role of quick and accurate diagnostics can thus not be overstated. As emphasised in preceding sections, diagnostic capabilities are sub-par in Africa but not totally absent. The session on laboratory and point of care tests created an opportunity for some functional mycology laboratories in Africa to share their approach to offering mycology diagnostic services despite limitations. The Lagos University Teaching Hospital diagnostic laboratory emphasized their focus on improving basic specimen processing and simple diagnostic tools such as microscopy and minimum requirements for fungal culture. The Centre for Healthcare-Associated, Antimicrobial Resistance and Mycoses (CHARM) team from South Africa’s National Institute for Communicable Diseases (NICD) shared their wealth of experience in antifungal sensitivity testing which is offered in a reference laboratory setting.

Rapid and point of care tests for fungal diseases (which allow for the detection of antigen or antibody depending on the disease) have come of age and are increasingly available in immunochromatographic and lateral flow formats, although access remains challenging in many parts of Africa. Massively rolling out these tests, through government-sponsored health insurance packages, to health facilities catering for at-risk populations could revolutionise mycology practice in the region since they satisfy the ASSURED criteria of ‘Affordability, Sensitivity, Specificity, User friendliness, Robustness, Equipment-free and Delivered’, to varying degrees.²⁶ Additional criteria proposed in 2019, namely real time connectivity and ease of sample collection/environmental friendliness, are particularly useful features for a point of care or rapid diagnostic test for IFDs. Real time connectivity could result in faster reporting of test results for prompt action while also encouraging better disease surveillance and quality assurance monitoring. Ease of sample collection is especially desirable in Africa where invasive sampling procedures such as lumbar punctures and bronchoalveolar lavage are seldom undertaken. Besides these desirable criteria, the need for clarity on who performs which test, where it is performed and how it is reported was discussed. With the exception of Aspergillus galactomannan lateral flow RDT which requires sample pre-treatment steps and some laboratory equipment, the other lateral flow assays like Crag and Aspergillus antibody tests could be conducted by all cadres of health worker provided they have been properly trained. Nevertheless, who performed the test and where it was conducted may differ depending on local context and this should be taken into consideration when assigning roles. The need for implementation research to determine the best way of operationalising the conduct of these tests in African settings was underscored. Finally, the use of RDTs does not obviate the need for quality assurance. Experienced laboratory personnel still need to provide oversight function irrespective of where the test is conducted to ensure there is no compromise to quality care and documentation. Future research and development in the field could be targeted at molecular point of care tests for IFDs as has been done for tuberculosis with the Xpert MTB/RIF and loop mediated isothermal amplification tests.

Capacity building programs and initiatives

In Africa, capacity building is required in the areas of clinical and laboratory personnel knowledge, laboratory infrastructure and networks as well as operating disease registries and conducting quality health research for IFDs. While many challenges remain, a few ongoing initiatives within the region and in regions with similar socioeconomic profiles are noteworthy and could serve as primers to catalyse action. An example of laboratory capacity building was presented from Morocco where the mycological panel in the diagnostic laboratory was gradually upgraded and adapted to local epidemiology and financial resources based on mapping of the expected fungal infections from medical units and patient populations.

In Nigeria, NIFUSCAB, with support from CDC, conducted clinician training to improve requests for mycological testing while also training laboratory scientists to conduct the tests and providing diagnostics, namely Crag LFA, Aspergillus galactomannan, Aspergillus antibody and Histoplasma enzyme immunoassay. This three-pronged approach (clinician training, laboratory personnel training and provision of diagnostic test kits) resulted in significant increases in testing for IFDs at the six sentinel sites. Furthermore, in order to reach a wider group of trainee doctors, NIFUSCAB has engaged the National Postgraduate Medical College of Nigeria to host training modules in the form of freely available online webinars on the College’s website. These webinars would be accessed by trainees and certificates of completion awarded after scoring a pass mark on the post-course assessment. At the time of the conference, NIFUSCAB was in the process of co-creating the webinars with indigenous specialists, a strategy expected to ensure buy-in from both trainers and trainees. Disease entities selected for development as modules were dependent on at-risk patient groups likely to be seen by each clinical specialty (Table 2). Diagnostic specialties, namely radiology and histopathology, which cut across all risk groups, were also targeted for module development.

Table 2:

Fungal diseases targeted for educational webinars based on at-risk groups seen by clinical specialties in Nigeria

Clinical specialty	Patient groups at risk	Fungal infections targeted for module development
Dermatology	Immunocompetent and PLHIV	Dermatomycosis: Tinea capitis; Tinea corporis; Onychomychosis Fungal neglected tropical diseases (mycetoma, chromoblastomycosis, sporotrichosis) Systemic mycoses: cyptococcosis, histoplasmosis
Infectious diseases	PLHIV	Candidiasis: Oral and oesophagal Cryptococcosis, Pneumocystosis Disseminated histoplasmosis
Intensive care	Central venous line in situ, Mechanical ventilation, COVID-19	Invasive candidiasis Invasive aspergillosis
Haemato-oncology	AML, HSCT, Cancer patients receiving radiotherapy	Invasive candidiasis Invasive aspergillosis Mucormycosis
Pulmonology	TB, COPD, Asthma	Chronic pulmonary aspergillosis Allergic bronchopulmonary aspergillosis
Otorhinolaryngology	Immunocompetent, Diabetic patients	Otomycosis Fungal invasive rhinosinusitis

PLHIV: Persons living with HIV; AML: Acute Myeloïd Leukemia; HSCT: Hematopietic stem cell transplantation; TB: Tuberculosis COPD: Chronic Obstructive Pulmonary Disease

Despite its importance, clinician training takes a long time to yield dividends and can be influenced by many variables, including the quality of the teaching system and health worker turnover/attrition rates.²⁷ As a stop-gap measure, diagnostic laboratory hubs (DLH) have the potential to significantly impact the diagnosis of key IFDs in certain target populations when implemented in settings where there is limited clinical expertise in fungal diseases. GAFFI established such a laboratory capacity building partnership in Guatemala, implementing a package of care to screen for cryptococcosis, histoplasmosis and tuberculosis in persons living with HIV. Specimens are sent in to the DLH from a network of laboratories. The centralization of tests at the DLH provides a cost-effective approach that assures the quality of a local laboratory service especially when the incidence of fungal diseases is relatively low. Results can be sent electronically to clinicians for prompt institution of therapy, thus improving outcomes.²⁷

Using eumycetoma as a case study, the mycetoma research centre (MRC), a WHO collaborating centre in Khartoum, Sudan emphasised the need to build capacity for research and development. Mycetoma was recognized as a neglected tropical disease in 2016.²⁸ Lack of access to diagnostics (i.e., trained microscopists, culture techniques, or PCR methods), the unavailability of a point-of-care test and effective antifungals for eumycetoma are some of the challenges faced in mycetoma care. Research and development priorities, thus include updating the global burden and mapping of cases; developing novel point of care tests for use in low resource settings, developing new treatment solutions including drug discovery and susceptibility testing, ascertaining the mode of transmission and determining the role of the host and the pathogen in mycetoma. To date, itraconazole is the only drug used for mycetoma treatment because despite good in vitro activity of voriconazole and posaconazole, their use is limited by longer treatment duration, high cost, and the relative lack of studies regarding their response.²⁸ A landmark achievement of the MRC was the recent conclusion of a clinical trial comparing the efficacy of fosravuconazole, a prodrug of ravuconazole, to itraconazole for treatment of eumycetoma. This double-blinded, randomized clinical trial sponsored by the Drugs for Neglected Diseases Initiative (DNDi) and partners, is the first of its kind in mycetoma research.²⁹ The trial demonstrated no significant difference in efficacy rates between both drugs. However, forsavuconazole offers several advantages over itraconazole like reduced pill burden, once weekly dosing, and minimal drug-drug interactions, thus presenting a more patient-friendly option for mycetoma treatment. Challenges to building research capacity and conducting the trial in Africa were highlighted by the delegate representing DNDi including the civil unrest on-going in Sudan.

Synopsis of technical sessions

Despite pervasive challenges- lack of tools, trainings and surveillance- improving the field of medical mycology in Africa is possible with concerted efforts. Participants iterated the need for a change in the way research is conducted in Africa to include a wider scope of partners and the adoption of more robust methodologies. It was agreed that researchers need to partner with governments and civil society organisations to facilitate stakeholder buy-in. Similarly, to gain more insight and achieve greater impact, research methods need to incorporate health economics, social science and health systems strengthening. The relevant professionals from these disciplines should be part of research teams. Adequate investments in capacity building for health workers and access programmes are also needed before embarking on research. This enables the smooth uptake of research findings and swift adoption of evidence into practice. Notable mycology research collaborations driven by African leadership which embody these principles were highlighted including DREAMM,²⁵ and a National Institute for Health Research-funded Global Health Research Group on HIV-associated Fungal Infections (acronym: IMPRINT). The need to expand laboratory diagnostic access across the continent by embracing modern technologies from telemedicine to artificial intelligence was emphasised. Local manufacturing of point of care tests also requires broader consideration. The potential impact of establishing mycology reference laboratories at national or sub-regional levels was discussed in detail. These laboratories could serve as training centres, and given their robust organisational structure, they could serve as hubs for international collaboration within and outside the continent. However, reference laboratories stand the risk of becoming ‘ivory towers’ that fail to impact grassroot patient care. This is preventable by maintaining close links with and providing diagnostic support for a network of clinical or health facility laboratories.

Meeting resolutions - The Nairobi Declaration

At the close of the two-day meeting and based on the deliberations, the consortium agreed on the following action points:

1. To catalogue existing free online educational resources to accelerate the work of raising awareness about IFD. At the same time, country delegates and national societies will pursue local initiatives within country to raise awareness and conduct local training programmes.

2. To build strong collaborations between clinical and laboratory teams. The PAMWG will facilitate exchange programmes to build clinical and laboratory capacity to diagnose and treat IFDs. The group will undertake a detailed mapping of African reference laboratories and what they offer to provide information to clinicians and laboratorians seeking particular skillsets or capacities. Other facilities outside the continent, such as European Excellence Centres in Medical Mycology affiliated with ECMM and centres affiliated with ISHAM, would be similarly catalogued as possible resources for training.

3. To spearhead improved surveillance for IFDs at national and sub-regional levels. Best practices and lessons learned from current surveillance initiatives will be curated and used as advocacy, training and implementation blueprints for establishing sustainable systems in additional countries.

4. To champion advocacy for the provision of high-quality POC and conventional laboratory testing for IFDs using available tools such as the WHO Essential Diagnostics List and domesticated national versions of this list, and leveraging existing programmes such as HIV and TB treatment programmes.

5. To advocate for the availability of antifungals at the level of the African Union and Africa CDC as well as global funders such as Unitaid, Global Fund and US President’s Emergency Plan for AIDS Relief (PEPFAR).

6. To build research capacity especially for clinical trials and implementation science research that will further elucidate best practices for managing fungal diseases in Africa.

Progress made in realising these resolutions will be evaluated in the next biennial meeting.

Conclusion

Through this first scientific conference of the PAMWG, experts and enthusiasts from all over the continent collectively synthesised the state of the art of medical mycology in Africa. Despite numerous gaps and challenges related to knowledge, diagnosis and treatment, some African-led initiatives including NIFUSCAB and the Mycetoma Research Centre stood out as proof-of-concept models of what can be achieved in the continent through local leadership, regional collaboration and global support. Through the Nairobi declaration, delegates committed to galvanising action in a uniform direction. This is expected to address and provide sustainable solutions to the menace of neglected, life-threatening fungal diseases in Africa.