Excessive neutrophil recruitment promotes typical T-helper 17 responses in Coronavirus disease 2019 patients.

Coronavirus disease 2019 (COVID-19) is caused by a recently identified virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease is a pandemic. Although the hallmarks of severe COVID-19 have been established, the underlying mechanisms that promote severe pathology have not been thoroughly studied. A better understanding of the immune response in severe COVID-19 patients may help guide the development of therapeutic strategies and predict immuno-pathogenicity. This study was set to determine the lymphocyte and cytokine profiles associated with COVID-19 severity. A total of 43 hospitalised COVID-19 patients were recruited for the study and whole blood samples were drawn from each patient. Complete blood counts, lymphocyte subset profiles and C-reactive protein statuses of patients were determined. Cytometric bead array was performed to analyse the cytokine profiles of each patient. The demographic characteristics showed that the median age of the patients was 48.72 years, with an interquartile range from 40 to 60 years, and 69.77% of the patients were male. COVID-19 patients exhibited significantly low CD4+ lymphocyte expansion and leucocytosis augmented by elevated neutrophil and immature granulocytes. Stratification analysis revealed that reduced monocytes and elevated basophils and immature granulocytes are implicated in severe pathology. Additionally, cytokine results were noted to have significant incidences of interleukin 17A (IL-17A) expression associated with severe disease. Results from this study suggest that a systemic neutrophilic environment may preferentially skew CD4+ lymphocytes towards T-helper 17 and IL-17A promotion, thus, aggravating inflammation. Consequently, results from this study suggest broad activity immunomodulation and targeting neutrophils and blocking IL-17 production as therapeutic strategies against severe COVID-19.

The Identification and Characterization of Immunoreactive Fungal Proteins Recognized by Sera from Zimbabweans Sensitized to Fungi.

BACKGROUND: Exposure to fungal allergens poses a serious threat to human health, especially to mould-allergic individuals. The prevalence of fungal allergic disease is increasing globally but is poorly studied in Africa. Here, we aimed to identify and characterize fungal proteins that were immunoreactive against serum samples from fungal-sensitized Zimbabweans from Shamva district to inform the development of diagnostics and therapeutics. METHODS: Crude protein extracts of the Ascomycota Aspergillus fumigatus, Alternaria alternata, Cladosporium herbarum, Epicoccum nigrum, Penicillium chrysogenum, and Saccharomyces cerevisiae as well as mucoromycota Rhizopus nigricans were individually separated by one-dimensional gel electrophoresis for protein staining and immunoblotting. A pool of eight sera from fungi-sensitive Zimbabwean children aged 3-5 years was used to screen the crude extracts to determine their immunoreactivity. Protein bands recognized by the sera were subjected to mass spectrometry to identify the individual proteins reactive with the sera. RESULTS: The pooled serum sample reacted with 20 bands, which resolved to 34 distinct proteins, most of which were novel immunogens. The pool was most reactive to A. alternata. The proteins identified included peptidases (8/34), hydrolases (6/34), oxidoreductases (5/34), and glucosidases (4/34), while 11/34 were unknown. Eight of the proteins were predicted to be allergens using the Structural Database of Allergenic Proteins (SDAP). CONCLUSIONS: We identified novel immunogens from fungi expanding the number of known fungal allergens. These form a potential basis for diagnostics specific for the Zimbabwean population. Validation assays will now need to be carried out to further evaluate the cross-reactivity of the identified allergen candidates as well as investigate their potential recognition in a larger cohort of patients. Furthermore, there is now a need to conduct studies relating sensitization to these immunogens and clinical diseases in the population.

A mathematical model for the prediction of the prevalence of allergies in Zimbabwe.

BACKGROUND: The prevalence of allergies has been observed to be increasing in the past years in Zimbabwe. It is thus important to consider the long term prevalence of allergies. Our interest is in investigating the trends of allergies in the next 2 decades. METHOD: We formulate a deterministic model with 6 compartments to predict the prevalence of allergies in Zimbabwe. The human population is divided into 4 distinct epidemiological, classes based on their exposure to 2 allergen groups (food and inhalants), represented by 2 compartments. The model is used to predict the prevalence of allergen sensitization. The number of human allergen groups in each compartment are tracked through a system of differential equations. Model parameters were obtained by fitting observed data to the model. Graphical solutions of the model were developed using Matlab and Excel. RESULTS: The rate of sensitisation to food allergen sources is found to be lower than the rate of sensitisation to inhalant allergens. The rate at which individuals develop tolerance to food allergen sources is found to be almost twice the rate of developing tolerance to inhalant allergies. The equilibrium solutions (the long-term states of the populations) of the model are found to be non-zero implying that there will never be an allergy-free population. Our results also show that the prevalence of food allergy is likely to increase in the next 2 decades while inhalant allergy prevalence is expected to decrease. CONCLUSION: Our long-term solutions show endemicity in allergies in Zimbabwe. So, allergy will be endemic in the Zimbabwean population; hence there is a need for allergy care and management facilities to be increased. These results are critical in policy development and planning around allergies in the near future.

Fungal allergic sensitisation in young rural Zimbabwean children: Gut mycobiome and seroreactivity characteristics.

BACKGROUND: The prevalence of allergic diseases has increased over the last few decades, with sensitisation to fungal allergens and gut microbiome dysbiosis implicated in this trend. The fungal community in the gut (mycobiome) has yet to be characterised and related to fungal allergic sensitisation. Thus, we characterised the gut mycobiome and related it to fungal sensitisation and seroreactivity among Zimbabwean children. We further determined the effect of host age, sex, Schistosoma haematobium infection and mycobiome composition on fungal sensitisation and seroreactivity. METHODS: Using shotgun metagenomic sequencing, we characterised the gut microbiome of stool samples of 116 preschool aged children (PSAC) (≤5 years old, 57(49.1%) male and 59 (50.9%) female). Sensitisation to common fungi in Zimbabwe was assessed using skin prick tests (SPTs). Allergen-specific IgM, IgA, IgG, IgE and IgG4 antibodies were quantified by ELISA. We analysed the relationship between fungal genera and SPT reactivity by ANOVA; fungal genera and IgE antibody reactivity by linear regression; variation in mycobiome abundance with host and environmental factors by PERMANOVA; SPT reactivity and host and environmental factors by logistic regression; seroreactivity and host and environmental factors by ANOVA. RESULTS: The mycobiome formed <1% of the sequenced gut microbiome and 228 fungal genera were identified. The most abundant genera detected were Protomyces, Taphrina, and Aspergillus. S.haematobium infection had a significant effect on fungal genera. Prevalence of SPT sensitisation to ≥1 fungal species was 96%, and individuals were frequently sensitised to Saccharomyces cerevisiae. Antibodies were detected in 100% of the population. There was no relationship between mycobiome abundance and IgE titres or IgE/IgG4 ratios for each fungal species; no significant differences between SPT reactivity and abundance of fungal species except for S. cerevisiae; and fungal seroreactivity did not significantly differ with age. There were some sex (m>f for, Epicoccum nigrum and Penicillium chrysogenum) and SPT reactivity -related differences in seroreactivity. CONCLUSION: This is the first comprehensive characterisation of gut mycobiome and fungal allergic sensitisation of rural children in Zimbabwe. Although reported allergic disease is low there is a high percentage of sensitisation. Further studies with larger populations are required to understand the role of the mycobiome in allergic diseases.

Algorithm for asthma diagnosis and management at Chitungwiza Central Hospital, Zimbabwe.

INTRODUCTION: asthma is a chronic inflammatory and a heterogeneous condition of respiratory system whose pathogenesis is linked with variable structural changes. The clinical manifestation of asthma includes attacks of breathlessness, cough, chest tightness and wheezing. Provision of basic equipment and test for asthma diagnosis and access to essential medicines by asthmatic patients reduces morbidity and mortality rates. Significant progress has been made in the diagnosis and management of asthma in other countries but not in the health care delivery system in Zimbabwe. Therefore, the aim of this study was to develop algorithm for asthma diagnosis and management for Zimbabwe. METHODS: a two stage Delphi model was used to collect data in order to develop an algorithm of asthma diagnosis and management. A baseline interview with 44 doctors was done to understand their experiences and knowledge regarding asthma diagnosis and management. We collected data using the KoBo Collect Toolbox installed on Android mobile phone and transferred the data to an Excel 2016 spreadsheet for cleaning. The data was qualitatively analysed and themes were constructed. These themes were further explored in stage two at an algorithm development workshop which was led by 4 medical expert panellists in order to develop consensus on the information to be included in the algorithms for asthma diagnosis and management. A total of 15 doctors and 30 nurses participated at the workshop. RESULTS: doctors who attended the workshop described the challenges in asthma diagnosis and management that they experienced. These challenges were attributed to lack of basic equipment such as spirometers and Peak Expiratory Flow Meters and tests which included IgE tests, Skin Allergen Tests and RAST. Asthma diagnosis clinical history and management was based on the doctors' knowledge. The doctors indicated the need for refresher courses to update their knowledge on asthma diagnosis and enhance their diagnostic skills. A draft algorithm framework for asthma diagnosis was developed at the workshop and later refined by the core-research team. The final algorithm described in this paper was circulated for further contributions and endorsement by the asthma experts. CONCLUSION: we established the need for doctors to receive constant refresher courses on asthma diagnosis for upskilling. We recommend adoption by the Zimbabwe's Ministry of Health and Child Care of the asthma diagnostic algorithm we developed.

The Pathogenesis of Fungal-Related Diseases and Allergies in the African Population: The State of the Evidence and Knowledge Gaps.

The prevalence of allergic diseases in the African continent has received limited attention with the allergic diseases due to fungal allergens being among the least studied. This lead to the opinion being that the prevalence of allergic disease is low in Africa. Recent reports from different African countries indicate that this is not the case as allergic conditions are common and some; particularly those due to fungal allergens are increasing in prevalence. Thus, there is need to understand both the aetiology and pathogenies of these diseases, particularly the neglected fungal allergic diseases. This review addresses currently available knowledge of fungal-induced allergy, disease pathogenesis comparing findings from human versus experimental mouse studies of fungal allergy. The review discusses the potential role of the gut mycobiome and the extent to which this is relevant to fungal allergy, diagnosis and human health.

HIV/AIDS in Central Africa: pathogenesis, immunological and medical issues.

The estimated worldwide prevalence of human immunodeficiency virus (HIV) infections topped 52.5 million in June 2003, a mere 20 years after the aetiological agent was shown to be a sexually transmissible virus with a predilection for CD4+ T lymphocytes. More than 22 million people have died of the acquired immunodeficiency syndrome (AIDS) and the condition has in one generation become the most devastating and persistent epidemics in recorded history. More than two thirds of the world total of HIV-infected people live in Sub-Saharan Africa. In Central and Southern Africa at least 20% of the adult population is infected. As these adults die, they leave increasing numbers of orphans. Life expectancy at birth declined by 10 years per decade since the late 1980s to 50 years in the late 1990s, and in Botswana it is estimated to be as low as 33 years by 2010. The epidemic is increasing unabated and prospects for a curative or protective vaccine remain remote. The impact on HIV in Africa has been so profound that it influences political, economic, agriculture/food security, social, education, defence, science and health considerations. The medical and in particular immunology communities in Central Africa have the invidious challenge of on the one hand diagnosing the condition, monitoring its impact and contributing to treatment and management efforts. The science and clinical practice of immunology is challenged to find answers to the epidemic, perhaps including a vaccine. In this review we address the peculiarities of the HIV epidemic in Africa, its epidemiology and immunopathogenesis. We address the effect of the epidemic on individual patients, in their homes, workplaces and the knock-on effects on families and friends of the infected. Respective specialists discuss special groups (women, children) that are predominantly seen in Africa. We also discuss the impact of the epidemic on the clinical practice of medicine in general and challenges faced in the introduction of antiretroviral medicines. We also discuss options available for the diagnosis, treatment and monitoring of HIV-infected patients in this region.

Inhalant allergies in Zimbabwe: a common problem.

Allergic rhinitis, allergic conjunctivitis, allergic asthma and atopic dermatitis affect a quarter of the population of the industrialised countries and are the most common symptoms of type I hypersensitivity reactions. Their prevalence has been documented in many communities, yet data from Africa are limited. In the 5-year period from September 1997 to September 2002, approximately 14,000 patients of all ages were referred to the only specialist allergy clinic in Harare, Zimbabwe, for allergy investigation, diagnosis and therapeutic management. In approximately one tenth of these patients, food allergies were diagnosed; less frequent presentations included allergic pharyngitis, bee- or wasp-induced reactions and latex allergy. An allergologic basis for the clinical conditions was established following a careful clinical and physical examination, evaluation of family history and the detection of in vivo (skin prick test) or in vitro (radio-allergo-sorbent test; RAST) allergen-specific IgE antibodies to known sources of inhalant allergens, using commercial allergen extracts and a RAST assay kit. Asthma diagnosis was supported by the clinical and laboratory findings of salbutamol-reversible airways obstruction. Case files of the first 1,046 patients are reviewed in order to define the clinical presentation of allergic patients in this region. It is highlighted that allergy in general and inhalant allergy in particular are very common, if not widely acknowledged, clinical problems in this Central African region.