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.

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.

Clinical morbidity associated with Schistosoma haematobium infection in pre-school age children from an endemic district in Zimbabwe.

OBJECTIVE: To investigate Schistosoma haematobium morbidity in infected pre-school age children and establish their disease burden. METHODOLOGY: Pre-school age children (1-5 years) who were lifelong residents of the study area and had no other infections were included in the study. Participants underwent a physical examination with clinicians blinded to their infection status. Diagnosis of S. haematobium was by urine filtration. RESULTS: The prevalence of S. haematobium was 35.1% (146/416). The clinical features observed in patients with Schistosoma haematobium were as follows: wheezes (morbidity attributable factor (AF = 93.9%), haematuria (AF = 92.6%), ascites (AF = 91.5%), atopy (AF = 76.9%), inguinal lymphadenopathy (AF = 68.4%), stunting (AF = 38.2), malnutrition (MUAC)(AF = 20%) and weight for height scales (AF = 5%). Schistosoma. haematobium infected children were at greater odds ratio of presenting with inguinal lymphadenopathy (AOR)=99.2(95% CI 24.2 to 854.5), wheezes in the chest (AOR = 35.4 95% CI 15.3 to 94.2), Distended abdomen with ascites (AOR = 23.9 95% CI 11.4 to 54), haematuria (AOR = 12.6 95% CI 11.6 to 14.1), atopy history (AOR = 5.6 95% CI 1.85 to 20.2), malnutrition (AOR = 2.3 95% CI 1.4 to 3.2) and stunting (AOR = 1.9 95% CI 1.1 to2.7). CONCLUSION: The study is novel as it demonstrates for the first time clinical morbidity markers associated with S. haematobium infection in pre-school age children. Furthermore the study adds scientific evidence to the call for inclusion of pre-school age children in schistosomiasis control programmes. These morbidity markers highlight the need for early diagnosis and screening for S. haematobium in pre-school age children.

OBJECTIF: Etudier la morbidité de Schistosoma haematobium chez les enfants d'âge préscolaire infectés et établir sa charge de morbidité. MÉTHODOLOGIE: Les enfants d'âge préscolaire (1 à 5 ans) qui avaient toujours résidents de la zone d'étude et qui n'avaient pas d'autres infections ont été inclus dans l'étude. Les participants ont subi un examen physique avec des cliniciens en aveugle sur leur état d'infection. Le diagnostic de S. haematobium a été effectué par filtration d'urine. RÉSULTATS: La prévalence de S. haematobium était de 35,1% (146/416). Les caractéristiques cliniques observées chez les patients infectés par S. haematobium étaient: respiration sifflante (facteur attribuable à la morbidité (FA = 93,9%), hématurie (FA = 92,6%), ascite (FA = 91,5%), atopie (FA = 76,9%), lymphadénopathie inguinale (FA = 68,4%), retard de croissance ( AF = 38,2), malnutrition (MUAC) (AF = 20%) et poids pour les échelles de taille (AF = 5%). Les enfants infectés par S. haematobium présentaient un rapport de cotes plus élevé de présenter une lymphadénopathie inguinale (AOR) = 99,2 ; (IC95%: 24,2 à 854,5), respiration sifflante dans la poitrine (AOR = 35,4 ; IC95%: 15,3 à 94,2), abdomen distendu avec ascite (AOR = 23,9 ; IC95%: 11,4 à 54), hématurie (AOR = 12,6 ; IC95%: 11,6 à 14,1), antécédents d'atopie (AOR = 5,6 ; IC95%: 1,85 à 20,2), malnutrition (AOR = 2,3 ; IC95%: 1,4 à 3,2) et retard de croissance (AOR = 1,9 ; IC95%: 1,1 à 2,7). CONCLUSION: L'étude est nouvelle car elle démontre pour la première fois des marqueurs cliniques de morbidité associés à une infection à S. haematobium chez des enfants d'âge préscolaire. En outre, l'étude ajoute des données scientifiques à l'appel à l'inclusion des enfants d'âge préscolaire dans les programmes de lutte contre la schistosomiase. Ces marqueurs de morbidité mettent en évidence la nécessité d'un diagnostic précoce et d'un dépistage de S. haematobium chez les enfants d'âge préscolaire.

Validation of the global lung initiative 2012 multi-ethnic spirometric reference equations in healthy urban Zimbabwean 7-13 year-old school children: a cross-sectional observational study.

BACKGROUND: The 2012 Global Lung Function Initiative (GLI2012) provide multi-ethnic spirometric reference equations (SRE) for the 3-95 year-old age range, but Sub-Saharan African populations are not represented. This study aimed to evaluate the fit of the African-American GLI2012 SRE to a population of healthy urban and peri-urban Zimbabwean school-going children (7-13 years). METHODS: Spirometry and anthropometry were performed on black-Zimbabwean children recruited from three primary schools in urban and peri-urban Harare, with informed consent and assent. Individuals with a history or current symptoms of respiratory disease or with a body mass index-z score (BMI) < - 2 were excluded. Spirometry z-scores were generated from African-American GLI2012 SRE, which adjust for age, sex, ethnicity and height, after considering all GLI2012 modules. Anthropometry z-scores were generated using the British (1990) reference equations which adjust for age and sex. The African-American GLI2012 z-score distribution for the four spirometry measurements (FVC, FEV1, FEV1/FVC and MMEF) were evaluated across age, height, BMI and school (as a proxy for socioeconomic status) to assess for bias. Comparisons between the African-American GLI2012 SRE and Polgar equations (currently adopted in Zimbabwe) on the percent-predicted derived values were also performed. RESULTS: The validation dataset contained acceptable spirometry data from 712 children (344 girls, mean age: 10.5 years (SD 1.81)). The spirometry z-scores were reasonably normally distributed, with all means lower than zero but within the range of ±0.5, indicating a good fit to the African-American GLI2012 SRE. The African-American GLI2012 SRE produced z-scores closest to a normal distribution. Z-scores of girls deviated more than boys. Weak correlations (Pearson's correlation coefficient < 0.2) were observed between spirometry and anthropometry z-scores, and scatterplots demonstrated no systematic bias associated with age, height, BMI or socioeconomic status. The African-American GLI2012 SRE provided a better fit for Zimbabwean paediatric spirometry data than Polgar equations. CONCLUSION: The use of African-American GLI2012 SRE in this population could help in the interpretation of pulmonary function tests.

Association of Schistosoma haematobium infection morbidity and severity on co-infections in pre-school age children living in a rural endemic area in Zimbabwe.

BACKGROUND: Individuals living in Schistosoma haematobium endemic areas are often at risk of having other communicable diseases simultaneously. This usually creates diagnostic difficulties leading to misdiagnosis and overlooking of schistosomiasis infection. In this study we investigated the prevalence and severity of coinfections in pre-school age children and further investigated associations between S. haematobium prevalence and under 5 mortality. METHODS: A community based cross-sectional survey was conducted in Shamva District, Zimbabwe. Using random selection, 465 preschool age children (1-5 years of age) were enrolled through clinical examination by two independent clinicians for the following top morbidity causing conditions: respiratory tract infections, dermatophytosis, malaria and fever of unknown origin. The conditions and their severe sequels were diagnosed as per approved WHO standards. S. haematobium infection was diagnosed by urine filtration and the children were screened for conditions common in the study area which included HIV, tuberculosis, malnutrition and typhoid. Data was analysed using univariate and multinomial regression analysis and relative risk (RR) calculated. RESULTS: Prevalence of S. haematobium was 35% (145). The clinical conditions assessed had the following prevalence in the study population: upper respiratory tract infection 40% (229), fever of unknown origin 45% (189), dermatophytosis 18% and malaria 18% (75). The odds of co-infections observed with S. haematobium infection were: upper respiratory tract infection aOR = 1.22 (95% CI 0.80 to 1.87), dermatophytosis aOR = 4.79 (95% CI 2.78 to 8.25), fever of unknown origin aOR = 10.63 (95% CI 6.48-17.45) and malaria aOR = 0.91 (95% CI 0.51 to1.58). Effect of schistosomiasis coinfection on disease progression based on the odds of the diseases progressing to severe sequalae were: Severe pneumonia aOR = 8.41 (95% CI 3.09-22.93), p < 0.0001, complicated malaria aOR = 7.09 (95% CI 1.51-33.39), p = 0.02, severe dermatophytosis aOR = 20.3 (95% CI 4.78-83.20):p = 0.03, and fever of unknown origin aOR = 1.62 (95%CI 1.56-4.73), p = 0.02. CONCLUSION: This study revealed an association between schistosomiasis and the comorbidity conditions of URTI, dermatophytosis, malaria and FUO in PSAC living in a schistosomiasis endemic area. A possible detrimental effect where coinfection led to severe sequels of the comorbidity conditions was demonstrated. Appropriate clinical diagnostic methods are required to identify associated infectious diseases and initiate early treatment of schistosomiasis and co-infections in PSAC.

Possible association and co-existence of schistosome infection and prostate cancer: A systematic review.

Male genital schistosomiasis (MGS) may result in eggs lodged in the prostate causing persistent inflammation that may play a major role in prostate carcinogenesis. Globally, prostate cancer (PCa) is one of the most common cancers and the global distribution of PCa overlaps with that of schistosomiasis infections, suggesting a probable causal relationship. Objectives of this review were to assess evidence of co-existence of schistosomiasis and PCa and possible causal association between the two diseases. Relevant literature published between 1950 and 2019 yielded 20 publications on schistosomiasis and PCa co-existence. Schistosoma (S.) haematobium and S. mansoni were associated with MGS manifestation and mostly prostate adenocarcinoma diagnosis. Effects of prostatic MGS infection progressed over time with high Schistosoma egg burden thought to contribute to the development of PCa. Causal association and mechanistic pathways of MGS on PCa development and the role of Schistosoma eggs on the development of PCa remains unestablished.

HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a Polyclonal View.

HIV infections represent a major global health threat, affecting more than 35 million individuals worldwide. High infection rates and problems associated with lifelong antiretroviral treatment emphasize the need for the development of prophylactic and therapeutic immune intervention strategies. It is conceivable that insights for the design of new immunogens capable of eliciting protective immune responses may come from the analysis of HIV-specific antibody responses in infected patients. Using sophisticated technologies, several monoclonal neutralizing antibodies were isolated from HIV-infected individuals. However, the majority of polyclonal antibody responses found in infected patients are nonneutralizing. Comprehensive analyses of the molecular targets of HIV-specific antibody responses identified that during natural infection antibodies are mainly misdirected towards gp120 epitopes outside of the CD4-binding site and against regions and proteins that are not exposed on the surface of the virus. We therefore argue that vaccines aiming to induce protective responses should include engineered immunogens, which are capable of focusing the immune response towards protective epitopes.

Diagnostic options for pulmonary fungal diseases in Africa.

Background: Fungal lung diseases are global in distribution and require specific tests for diagnosis. We report a survey of diagnostic service provision in Africa. Methods: A written questionnaire was followed by a video conference call with each respondent(s) and external validation. To disseminate the questionnaire, a snowball sample was used. Results: Data were successfully collected from 50 of 51 African countries with populations >1 million. The questionnaire was completed by respondents affiliated with 72 health facilities. Of these 72 respondents, 33 (45.8%) reported data for the whole country while others reported data for a specific region/province within their country. In the public sector, chest X-ray and computed tomography are performed often in 49 countries (98%) and occasionally in 37 countries (74%), and less often in the private sector. Bronchoscopy and spirometry were done often in 28 countries (56%) and occasionally in 18 countries (36%) in the tertiary health facilities of public sector. The most conducted laboratory diagnostic assay was fungal culture (often or occasionally) in 29 countries (58%). In collaboration with the Africa Centre for Disease Control and Prevention, regional webinars and individual country profiles provided further data validation. Conclusion: This survey has found a huge disparity of diagnostic test capability across the African continent. Some good examples of good diagnostic provision and very high-quality care were seen, but this was unusual. The unavailability of essential testing such as spirometry was noted, which has a high impact in the diagnosis of lung diseases. It is important for countries to implement tests based on the World Health Organization Essential Diagnostics List.

Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-α 1,3-galactose.

BACKGROUND: The carbohydrate epitope galactose-α 1,3-galactose (α-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that α-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). OBJECTIVE: We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and α-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. METHODS: Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with α-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and α-Gal was analyzed by means of ELISA. RESULTS: Among the 47 parasite-infected patients, 85% had IgE antibodies against α-Gal (OD; median, 0.175; range, 0.102-1.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.103-1.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and α-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and α-Gal (P < .001). Among the group with cat allergy, only 5 patients had IgE to α-Gal, and nearly 75% (n = 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kU(A)/L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P < .05) but no correlation between CDE and Fel d 5 and α-Gal. CONCLUSION: IgE to α-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/allergy in parasite-infested areas.

Sensitisation to Imbrasia belina (mopane worm) and other local allergens in rural Gwanda district of Zimbabwe.

BACKGROUND: The prevalence of allergic diseases is increasing in Zimbabwe and the data relate to local as well as exotic allergen sources. As entomophagy, the practice of eating insects, is a recognised source of local allergens, we sought to measure the prevalence of and risk factors for sensitisation to Imbrasia belina (mopane worm), a popular edible insect. This was investigated alongside other locally relevant allergens in a rural community in Gwanda district, south of Zimbabwe. METHODS: A cross sectional study was conducted among 496 adults and children aged 10 years and above in Gwanda district, a mopane worm harvesting area in Zimbabwe. Data on individual characteristics and mopane worm exposure factors were collected using questionnaires. Sensitivity to allergens was assessed by performing skin prick tests at a local clinic using 10 different commercial allergen extracts (Stallergenes, France) and in-house extracts of mopane worm (Imbrasia belina) and mopane leaves (Colophospermum mopane). Data were analysed using Stata version 13 software. RESULTS: The prevalence of sensitisation to at least one allergen was 31.17% (n = 144). The prevalence of atopy was higher in adults (33.33%) than in children (23.53%) (p = 0.059). The commonest inhalant allergen sources were mopane worm (14.29%), Tyrophagus putrescentiae (14.29%), mopane leaves (13.42%), Alternaria alternata (6.49%) and Dermatophagoides pteronyssinus (6.49%). Polysensitisation was demonstrated in the study population and of the 108 participants (75%) who were sensitised to two or more allergens, 66 (61%) were women. Sensitisation to mopane worm and mopane leaves often clustered with Tyrophagus putrescentiae amongst adults. Adjusted logistic regression analyses between mopane worm sensitisation and self-reported exposure variables showed that sensitisation was more likely amongst mopane worm harvesters (OR = 1.92, 95%CI = 0.77-4.79), those who cooked or roasted mopane worms during harvesting (OR = 2.69, 95%CI = 0.78-9.31) and harvesting without personal protective equipment (PPE) (OR = 2.12, 95%CI = 0.83-5.44) compared to non-harvesters. CONCLUSION: Atopic sensitization was common in this mopane worm harvesting community in Gwanda district of Zimbabwe. There was frequent co-sensitisation of mopane worm and mopane leaves with Tyrophagus putrescentiae in children and adults. It is important to determine the clinical relevance of our findings, particularly relating to mopane worm sensitisation.

Assessment of Anti m-RNA SARS-CoV-2 (BNT162b2) Antibody Titres in Mother and Child Pairs of Breastfeeding Women Vaccinated Post-Delivery.

The global response to the COVID-19 pandemic has been successfully driven by efforts to ramp up access to vaccines. Pregnant or breastfeeding women and their children have not benefited from the vaccines despite their susceptibility to the virus. We investigated whether women who were offered vaccination after delivery passively transferred protective antibodies to their infants via breast milk. Serum was collected from breast feeding mother-infant pairs and analysed for levels of antibodies to the SARS-CoV-2 spike protein using the CLIA chemiluminescence technique. Data were analysed for the significance of the differences using the Mann-Whitney U test and the Spearman's rank correlation coefficient to determine the strength of the correlation. A total of 13 mothers, mean age 34.86 (95%CI = 33.21-36.48) years and their infants, mean age 15.77 (95%CI = 11.24-20.29) months were enrolled. The mothers had completed their courses of the mRNA BNT162b2 SARS-CoV-2 vaccine during breastfeeding, 8.3 (95%CI = 7.24-9.36) months before the study. All 13 mothers had detectable antibodies to the SARS-CoV-2 spike protein, mean 1252, (95%CI = 736-1769) BAU/mL. Antibodies were detected in 3/13 (23%) breast-fed infants mean 322, (95%CI = 252-897) BAU/mL. There was no correlation between the maternal and infant IgG antibody titres. The time-lag since full vaccination did not correlate to the presence of antibodies in infant sera. Maternal or infant ages did not correlate to the presence of antibodies. Although some children (23%) had anti-SARS-CoV-2 antibodies, there was no association between vaccine-induced COVID-19 spike protein specific maternal IgG antibody titres and the presence of antibodies in the breastfed infants. The data show that the transfer of passive immunity to infants following post-partum vaccination with the mRNA BNT162b2 SARS-CoV-2 vaccine may be infrequent in this population.

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.

Protocol for a scoping review to evaluate the extent of utilisation of healthcare services by asthma patients in sub-Saharan African countries.

INTRODUCTION: Health systems in sub-Saharan African (SSA) countries are fragile and centralised. Consequently, majority of people have restricted access to healthcare services. Given the rise in the prevalence and burden of asthma in SSA, it is imperative to scrutinise the utilisation of healthcare services by people with asthma. We aim to understand, through this review, the extent of utilisation of healthcare services by asthma patients in SSA countries. METHODS AND ANALYSIS: Arksey and O'Malley's scoping review methodology framework will be used to guide the conduct of this scoping review. We will conduct a search of the literature on the electronic databases: Medline, (using PubMed interface), EMBASE, EBSCOHOST, Web of Science and Google Scholar, grey literature sources and the reference lists of key studies to identify studies appropriate for inclusion. Two reviewers will independently screen all abstracts and full-text studies for inclusion. Registration of the proposed scoping review on the PROSPERO has indicated that no similar work has been or is being done elsewhere. We will review studies published on the subject from January 2009 to May 2020 in SSA. ETHICS AND DISSEMINATION: The proposed scoping review will contribute towards the knowledge base on utilisation of healthcare services particularly for people with asthma. This will provide a better understanding of the extent of utilisation of healthcare services by asthma patients and ultimately contribute to improvement of quality of care for people suffering from asthma. The results from the review will enlighten and guide healthcare practitioners and researchers on developing appropriate and feasible interventions to increase the utilisation of healthcare services by asthma patients in resource-constrained settings in SSA countries. Results of this scoping review will be disseminated through a peer-reviewed publication, conference presentations and a 1-day stakeholder meeting. PROSPERO REGISTRATION NUMBER: CRD42020154127.

A feasibility study to assess Imbrasia belina (mopane worm) sensitisation and related respiratory health outcomes in a rural community in Gwanda district, Zimbabwe.

BACKGROUND: Allergic diseases are considered to be some of the fastest growing chronic conditions in Africa. Of concern is the paucity of knowledge about the local environment and its role in allergic disease development. In response to this, we explored whether Imbrasia belina, a popular indigenous edible insect commonly known as mopane worm, is a potential allergen of clinical and public health significance in Zimbabwe. This study was intended to assess the plausibility and feasibility of this hypothesis with a view to evaluate the insect's health impact in a larger study. METHODS: The study participants included male and female villagers aged 10 years and above in Gwanda district, Zimbabwe. Eligible participants who completed the household questionnaire were referred to the local clinic for skin prick tests and to measure lung function and allergic airway inflammation. Allergen sensitisation patterns were evaluated using 10 different inhalant allergen extracts including an in-house preparation of mopane worm. Lung function was measured with a Koko Legend spirometer, and fractional exhaled nitric oxide levels (FeNO) (NIOX VERO) were measured in participants with at least one abnormal spirometric parameter. Data was analysed using Stata version 13 software. RESULTS: Of the 46 eligible participants that completed the household questionnaire, 17 went to the clinic giving a response rate of 37%. The majority who completed the questionnaire were adults (91%) and the children (9%) were all female. The prevalence of sensitisation to Imbrasia belina was 50%, and the prevalence ranged from 22 to 72% for the other allergens including cockroach, mosquito and house dust mites. The data collection tools were safe and well tolerated by participants with no adverse events reported. Self-reported respiratory symptoms, abnormal lung function and elevated FeNO were recorded amongst participants sensitised to mopane worm. CONCLUSION: Pre-defined feasibility criteria were met with the exception of a lower than expected response rate for clinic data collection in this pilot study. For the main study, modifying the sampling strategy and applying more consistent community engagement will improve the response rates.

Systemic Sclerosis in Zimbabwe: Autoantibody Biomarkers, Clinical, and Laboratory Correlates.

Introduction: Systemic sclerosis (SScl) is an autoimmune disease whose prevalence is rarely reported in Africa. Autoantibodies are the biomarkers of the condition, precede overt disease and determine disease phenotypes. SSc specific autoantibodies also vary between racial groupings. Objective: To investigate the clinical and laboratory characteristics of Zimbabwean patients who were reactive SSc specific autoantibodies. Materials and Method: 240 patients, 173 of them female with SSc specific autoantibodies were included. Autoantibodies were detected by indirect immunofluorescence microscopy and immunoblotting using a panel of 13 SScl (Euroimmun Ag., Germany). Demographic, clinical and laboratory parameters relevant to the monitoring of SScl were captured. These included pulmonary function tests, hematology, clinical chemistry, serology and thyroid function tests. Allergy skin prick tests (SPT) to inhalant and food allergen sources were conducted when indicated. Results: All the 240 patients (median age was 36 years) expressed SSc specific autoantibodies. 86% were Black, 11% White and 3% Asian and a fifth (20%) were younger than 16 years. Eleven (4.6%) fulfilled the ACR/EULAR classification of SSc. Clinically they had limited cutaneous (n=6), diffuse cutaneous (n=3) and SScl/inflammatory myopathy overlap (n=2). The most frequently detected antibodies anti-RNA polymerase III (RNAP) 55%, anti-Th/To (28%) anti-RNAP 11 (22%), anti-CENPB (18%) and anti-Scl-70/ATA (13%). Racial variations in the expression of these antibodies were apparent between Black, White and Asian patients. The majority (95%), who did not fulfil the ARA/EULAR criteria were symptomatic. Raynaud's Phenomenon was documented in 24%. Respiratory symptoms included coughing, dyspnea and wheezing. There was a restrictive ventilatory defect with increased FEV1/FVC ratio. Pruritus, urticaria and skin depigmentation were the main cutaneous features while constipation, bloating, Gastroesophageal reflux disease (GERD) and abdominal pain dominated GI symptoms. Mean blood pressure readings while normal varied with biomarkers. Haematology and biochemistry parameters were within normal reference ranges. Conclusion: The expression of SSc specific autoantibodies is common and associated with known SSc symptoms. The types and frequency of autoantibodies varied with racial groupings. A fifth of the patients were children below the age of 16 years.

Determining the burden of fungal infections in Zimbabwe.

Zimbabwe currently faces several healthcare challenges, most notably HIV and associated infections including tuberculosis (TB), malaria and recently outbreaks of cholera, typhoid fever and COVID-19. Fungal infections, which are also a major public health threat, receive considerably less attention. Consequently, there is dearth of data regarding the burden of fungal diseases in the country. We estimated the burden of fungal diseases in Zimbabwe based on published literature and 'at-risk' populations (HIV/AIDS patients, survivors of pulmonary TB, cancer, chronic obstructive pulmonary disease, asthma and patients receiving critical care) using previously described methods. Where there was no data for Zimbabwe, regional, or international data was used. Our study revealed that approximately 14.9% of Zimbabweans suffer from fungal infections annually, with 80% having tinea capitis. The annual incidence of cryptococcal meningitis and Pneumocystis jirovecii pneumonia in HIV/AIDS were estimated at 41/100,000 and 63/100,000, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) was 2,739/100,000. The estimated burden of fungal diseases in Zimbabwe is high in comparison to other African countries, highlighting the urgent need for increased awareness and surveillance to improve diagnosis and management.

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.

SARS-CoV-2 Serological testing in frontline health workers in Zimbabwe.

BACKGROUND: In order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient facing health workers. Our first aim was to determine both the infection status and seroprevalence of SARS-CoV-2 in health workers. Our second aim was to evaluate the occupational and demographic predictors of seropositivity to inform the country's infection prevention and control (IPC) strategy. METHODS AND PRINCIPAL FINDINGS: We invited 713 staff members at 24 out of 35 health facilities in the City of Bulawayo in Zimbabwe. Compliance to testing was defined as the willingness to uptake COVID-19 testing by answering a questionnaire and providing samples for both antibody testing and PCR testing. SARS-COV-2 antibodies were detected using a rapid diagnostic test kit and SAR-COV-2 infection was determined by real-time (RT)-PCR. Of the 713 participants, 635(89%) consented to answering the questionnaire and providing blood sample for antibody testing while 560 (78.5%) agreed to provide nasopharyngeal swabs for the PCR SARS-CoV-2 testing. Of the 635 people (aged 18-73) providing a blood sample 39.1% reported a history of past COVID-19 symptoms while 14.2% reported having current symptoms of COVID-19. The most-prevalent co-morbidity among this group was hypertension (22.0%) followed by asthma (7.0%) and diabetes (6.0%). The SARS-CoV-2 sero-prevalence was 8.9%. Of the 560 participants tested for SARS-CoV-2 infection, 2 participants (0.36%) were positive for SAR-CoV-2 infection by PCR testing. None of the SARS-CoV-2 antibody positive people were positive for SAR-CoV-2 infection by PCR testing. CONCLUSION AND INTERPRETATION: In addition to clinical staff, several patient-facing health workers were characterised within Zimbabwe's health system and the seroprevalence data indicated that previous exposure to SAR-CoV-2 had occurred across the full spectrum of patient-facing staff with nurses and nurse aides having the highest seroprevalence. Our results highlight the need for including the various health workers in IPC strategies in health centres to ensure effective biosecurity and biosafety.

Harmonizing allergy care-integrated care pathways and multidisciplinary approaches.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the "second translational gap". A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care. We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers. The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.