Cryptococcosis in Africa: What the data tell us.

Cryptococcosis is a neglected tropical disease and the main cause of fungal-related deaths in HIV-positive persons in Africa. It is an AIDS-defining illness that has almost surpassed tuberculosis (TB) in mortality despite wide coverage with antiretroviral therapy. What is known about the cryptococcosis burden in Africa is from estimations based on data from a few studies on the infection burden and associated complications. Consequently, the projected implications of cryptococcosis in Africa have been based on these estimations. This systematic review is aimed at providing unique and up-to-date data on the burden of cryptococcosis in Africa using published hospital-based research data on cryptococcosis in HIV infected and uninfected persons. The review also focused on providing temporal data on the availability of diagnostic and therapeutic options for cryptococcosis in Africa. From our results, about 40 948 cases of cryptococcosis were reported in Africa from 1969 to 2021, and the highest prevalence of cryptococcosis was from southern Africa. The most isolated species was Cryptococcus neoformans 42.4% (17 710/41 801) and only 1.3% (549/41 801) isolates were C. gattii. C. neoformans (serotype A) VN I 64.5% (918/1522) was the most prevalent serotype in Africa, while C. gattii (serotype C) VG IV was thought to pose a huge danger. However, C. neoformans (serotype A) VN I continued to be the major threat in Africa. Due to the limited availability of molecular typing methods and the widespread use of culture, direct microscopy, and serological techniques for diagnosis, 23 542 isolates were uncharacterised. Amphotericin B and flucytosine combination therapy is highly recommended for treatment of cryptococcal meningitis. However, these drugs are expensive and remain largely unavailable in most African countries. Amphotericin B requires laboratory facilities to monitor for toxicity. Although fluconazole monotherapy is the readily available treatment option for cryptococcosis, drug resistance, and high mortality have been recorded in majority of cases in Africa. The lack of awareness and paucity of published data on cryptococcosis are likely to have contributed to the underestimation of cases in Africa and led to underprioritisation of this important disease.

Cryptococcosis is a neglected tropical disease that manifests greatly in immunocompromised persons especially those with HIV infection. Our data show that managing cryptococcosis will require an integrated multidisciplinary approach that should include the utilisation of cryptococcal antigen (CrAg) testing, which is highly sensitive and cost-effective for diagnosing this disease.

The clinical spectrum of aspergillosis in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. In this review, we present the clinical spectrum and pathogenesis of syndromes caused by Aspergillus in COPD namely invasive aspergillosis (IA), community-acquired Aspergillus pneumonia, chronic pulmonary Aspergillosis and Aspergillus sensitisation. Some of these entities are clearly linked to COPD, while others may coexist, but are less clearly liked directly to COPD. We discuss current uncertainties as these pertain to IA in COPD cohorts and explore areas for future research in this field.

Phytochemical composition, bioactive properties, and toxicological profile of Tetrapleura tetraptera.

The use of medicinal plants has gained renewed wide popularity in Africa, Asia, and most parts of the world because of the decreasing efficacy of synthetic drugs. Thus, natural products serve as a potent source of alternative remedy. Tetrapleura tetraptera is a medicinal plant with cultural and traditional significance in West Africa. In addition to the plant being commonly used as a spice in the preparation of traditional spicy food for postpartum care it is also widely used to constitute herbal concoctions and decoctions for treatment of diseases. This review aimed to provide an up-to-date information on the ethnomedicinal uses, pharmacological activities and phytoconstituents of T. tetraptera. Preclinical studies regarding the plant's toxicity profile were also reviewed. For this updated review, literature search was done on PubMed, Science Direct, Wiley, and Google Scholar databases using the relevant keywords. The review used a total of 106 papers that met the inclusion criteria from January 1989 - February 2022 and summarised the bioactivities that have been reported for the rich phytoconstituents of T. tetraptera studied using various chemical methods. Considering the huge report, the review focused on the antimicrobial and antiinflammatory activities of the plant extracts and isolated compounds. Aridan, aridanin and several bioactive compounds of T. tetraptera have shown pharmacological activities though their mechanisms of action are yet to be fully understood. This study also highlighted the influence of plant parts and extraction solvents on its biological activities. It also presented data on the toxicological profile of the plant extracts using different models. From cultural uses to modern pharmacological research the bioactive compounds of T. tetraptera have proved effective in infectious disease management. We hope that this paper provided a robust summary of the biological activities and toxicological profile of T. tetraptera, thus calling for more research into the pharmacological and pharmacokinetic activities of natural products to help combat the growing threat of drug resistance and provide guidelines for their ethnomedicinal uses.

Recent advances and challenges in the early diagnosis and management of invasive fungal infections in Africa.

Invasive fungal infections are a serious concern globally, especially in African settings which are typified by poorly funded and fragile healthcare systems. Low performance diagnostics, limited therapeutics and poor societal awareness of invasive fungal infections are some of the perennial challenges which have contributed to the unacceptably high death rates from these serious infections. However, recent advances have been recorded in fungal diagnostics and therapeutics development. Research into the development of vaccines to prevent fungal disease is beginning to yield promising results. Here we highlight key successes recorded and gaps in this journey and argue that national governments and relevant stakeholders need to do more to prioritise invasive fungal infections. Pragmatic and context-specific measures are proposed to mitigate the peculiar challenges Africa faces in tackling invasive fungal infections.

Advancing disease genomics beyond COVID-19 and reducing health disparities: what does the future hold for Africa?

The COVID-19 pandemic has ushered in high-throughput sequencing technology as an essential public health tool. Scaling up and operationalizing genomics in Africa is crucial as enhanced capacity for genome sequencing could address key health problems relevant to African populations. High-quality genomics research can be leveraged to improve diagnosis, understand the aetiology of unexplained illnesses, improve surveillance of infectious diseases and inform efficient control and therapeutic methods of known, rare and emerging infectious diseases. Achieving these within Africa requires strong commitment from stakeholders. A roadmap is needed to guide training of scientists, infrastructural development, research funding, international collaboration as well as promote public-private partnerships. Although the COVID-19 pandemic has significantly boosted genomics capacity in Africa, the continent still lags other regions. Here, we highlighted key initiatives in genomics research and efforts to address health challenges facing the diverse and fast-growing populations on the continent. We explore the scalability of genomic tools and techniques to tackle a broader range of infectious diseases in Africa, a continent that desperately requires a boost from genomic science.

Emergomycosis in Africa: Time to Pay Attention to This Emerging Deadly Fungal Infection.

Emergomycosis is an emerging deadly infectious disease caused primarily by a little-known airborne pathogen Emergomyces africanus, which can cause clinical management challenge especially in patients with advanced HIV disease. This minireview describes Es. africanus as the main cause of emergomycosis in Africa as well as considers contributing factors to the difficulties encountered in managing this infection. Emergomycosis is common in HIV-positive persons with low CD4 lymphocyte count and has an estimated fatality of 50%. The infection exhibits airborne transmission with pulmonary and extrapulmonary manifestations leading to skin lesions. However, the pathogenesis of Es. africanus is still poorly understood. The management of the infection is complicated due to lack of defined diagnostic and therapeutic guidelines. Limited expertise, poor research funding, and lack of awareness and national surveillance are thought to impact the recognition and prioritisation of the infection. These factors may ultimately assign emergomycosis a 'neglected infection status' even as it is suspected to be prevalent in more African countries than previously recognised. Increased awareness and integrated and targeted strategies such as mobilising manpower in clinical mycology are of paramount importance in managing emergomycosis in Africa and beyond.

The impact of COVID-19 pandemic on invasive fungal infections in Africa: What have we learned?

Invasive fungal infections (IFIs) have been described as diseases of the poor. The mortality rate of the infections is comparable to that of malaria, HIV, and TB, yet the infections remain poorly funded, neglected in research, and policy at all levels of human resources. The Coronavirus Disease 2019 (COVID-19) pandemic has further worsened the current state of management for IFIs. At the same time, response to COVID-19 has stirred and boosted vaccine production, vaccine substance manufacturing, and building of next-generation sequencing capacity and genomics data sharing network in the continent. Through collaboration and transdisciplinary research effort, these network and technology can be extended to encourage fungal research to address health issues of existing and emerging fungal pathogens.

Integrated healthcare approach can curb the increasing cases of cryptococcosis in Africa.

Cryptococcosis is a neglected tropical infection and a major cause of morbidity and mortality, especially in HIV-positive persons in Africa. Efforts to manage HIV infection have not had any significant impact on the fatalities due to cryptococcosis. An integrated healthcare approach that includes universal care coverage for Africans, expanded national care guidelines to include CrAg screening for vulnerable groups in all African countries, collaborative research, infection surveillance, and data sharing within Africa will mark a turnaround point.

Invasive candidiasis in Africa, what is the current picture?

Invasive candidiasis is a serious, progressive, and potentially deadly infection that can affect the brain, heart, bones, eyes, and other parts of the body. It is associated with risk factors such as the use of indwelling medical devices, prolonged hospital stay, and broad-spectrum antibiotics use. It is especially seen in immunocompromised individuals such as patients with prolonged hospital stay, gastrointestinal surgery, haematological malignancies, and respiratory diseases. We have conducted a systematic search of literature using a select group of databases and appropriate search words and found that in Africa, there are 18 293 documented/reported cases of invasive candidiasis in the last few decades (1976-2021) and 16 636(91%) were cases of candidaemia. South Africa had the highest number of reported cases-15 002(82%), which may be due to underreporting of cases in other countries. HIV positive persons with invasive candidiasis in Africa accounted for 1 052(5.8%). Candida albicans was the most frequently isolated species 6 328(32.6%), followed by Candida parapsilosis 5 910(30.4%), and Candida auris 1 505(7.8%). Due to the affordability and availability of blood culture, it was used for diagnosis in most of the studies examined, while a few studies combined other techniques and just three studies from two countries used serological tests. Echinocandins are recommended as first-line therapy but are only available in 12 countries and are highly priced. The use of fluconazole, because of its availability and relatively inexpensive nature, has led to increased resistance of Candida species to the drug.

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.

Fungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses.

Candida species are part of the normal flora of humans, but once the immune system of the host is impaired and they escape from commensal niches, they shift from commensal to pathogen causing candidiasis. Candida albicans remains the primary cause of candidiasis, accounting for about 60% of the global candidiasis burden. The cell wall of C. albicans and related fungal pathogens forms the interface with the host, gives fungal cells their shape, and also provides protection against stresses. The cell wall is a dynamic organelle with great adaptive flexibility that allows remodeling, morphogenesis, and changes in its components in response to the environment. It is mainly composed of the inner polysaccharide rich layer (chitin, and ß-glucan) and the outer protein coat (mannoproteins). The highly glycosylated protein coat mediates interactions between C. albicans cells and their environment, including reprograming of wall architecture in response to several conditions, such as carbon source, pH, high temperature, and morphogenesis. The mannoproteins are also associated with C. albicans adherence, drug resistance, and virulence. Vitally, the mannoproteins contribute to cell wall construction and especially cell wall remodeling when cells encounter physical and chemical stresses. This review describes the interconnected cell wall integrity (CWI) and stress-activated pathways (e.g., Hog1, Cek1, and Mkc1 mediated pathways) that regulates cell wall remodeling and the expression of some of the mannoproteins in C. albicans and other species. The mannoproteins of the surface coat is of great importance to pathogen survival, growth, and virulence, thus understanding their structure and function as well as regulatory mechanisms can pave the way for better management of candidiasis.

A review on the traditional uses, phytochemistry, and pharmacological activities of clove basil (Ocimum gratissimum L.).

In traditional medicine, Ocimum gratissimum (clove basil) is used in the treatment of various diseases such as diabetes, cancer, inflammation, anaemia, diarrhoea, pains, and fungal and bacterial infections. The present study reviewed the phytochemicals, essential oils, and pharmacological activities of O. gratissimum. The bioactive compounds extracted from O. gratissimum include phytochemicals (oleanolic acid, caffeic acid, ellagic acid, epicatechin, sinapic acid, rosmarinic acid, chlorogenic acid, luteolin, apigenin, nepetoidin, xanthomicrol, nevadensin, salvigenin, gallic acid, catechin, quercetin, rutin, and kaempfero) and essential oils (camphene, ß-caryophyllene, α- and ß-pinene, α-humulene, sabinene, ß-myrcene, limonene, 1,8-cineole, trans-ß-ocimene, linalool, α- and δ-terpineol, eugenol, α-copaene, ß-elemene, p-cymene, thymol, and carvacrol). Various in vivo and in vitro studies have shown that O. gratissimum and its bioactive constituents possess pharmacological properties such as antioxidant, anti-inflammatory, anticancer, hepatoprotective, antidiabetic, antihypertensive, antidiarrhoeal, and antimicrobial properties. This review demonstrated that O. gratissimum has a strong preventive and therapeutic effect against several diseases. The effectiveness of O. gratissimum to ameliorate various diseases may be attributed to its antimicrobial and antioxidant properties as well as its capacity to improve the antioxidant systems. However, despite the widespread pharmacological activities of O. gratissimum, further experiments in human clinical trial studies are needed to establish effective and safe doses for the treatment of various diseases.