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.

The healthcare seeking behaviour of adult patients with asthma at Chitungwiza Central Hospital, Zimbabwe.

BACKGROUND: Although asthma is a serious public health concern in Zimbabwe, there is lack of information regarding the decision to seek for healthcare services among patients. This study aimed to determine the health care seeking behaviour of adult patients with asthma attending Chitungwiza Central Hospital in Zimbabwe. METHODS: A cross-sectional study was conducted among 400 patients with asthma. A questionnaire with four thematic areas (i) patients' demographic characteristics, (ii) types of health seeking behaviours (iii) knowledge of asthma treatment and (iv) attitudes on asthma treatment was used. RESULTS: We determined the sequence of remedial action that people undertake to rectify perceived ill health commonly referred to as health care seeking behaviours in 400 adult patients with asthma. This behaviour was considered good if the patient sought care at the hospital/clinic and or private practitioners. Poor health seeking behaviour was adjudged if patients sought no treatment, self-treated or resorted to traditional or faith healers for care.The majority 261(65.3%) of the study participants were females mainly between ages 29-39 years who lived in the urban setting. Distance to health facility, perception of supportive roles of healthcare providers, perceived good quality of service and knowledge of asthma complications were key determinants for health seeking behaviour. The results showed that majority 290 (72.5%) reported good health seeking behaviour. The correlates of good health seeking behaviour included financial capacity to pay for medical care [OR: 0.50 (CI: 0.31-0.83); p = 0.008)] and receiving good quality of asthma treatment [OR: 0.59 (CI: 0.37-0.93); p = 0.03)]. The inability to voluntarily seek own asthma treatment [OR: 1.68 (CI: 1.05-2.70); p = 0.03) was a significant risk factor (68% more likely) for poor health seeking behaviour. CONCLUSIONS: We concluded that prior to scaling up asthma treatment programmes in Zimbabwe, there is need to address, individual-level, community-level and health service level barriers to health seeking among asthma patients.

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.

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.

Development of a framework for increasing asthma awareness in Chitungwiza, Zimbabwe.

BACKGROUND: Asthma accounts for significant global morbidity and health-care costs. It is still poorly understood among health professionals and the general population. Consequently, there are significant morbidity and mortality rates throughout the globe. The aim of this study was to develop a framework to increase asthma awareness at Chitungwiza Hospital, Zimbabwe. METHODS: A modified Delphi model was used to collect data to develop a framework for increasing asthma awareness. At baseline (round 1) in-depth interviews with 44 medical doctors were carried out to understand the level of asthma awareness. Round 2 data collection was in the form of a workshop involving a total of 15 doctors, 30 nurses, four public relations officers, and two health education and promotion officers. The same participants who were engaged in round 2 were also involved in the third round where consensus was achieved by the health professionals. RESULTS: Our study showed that awareness to asthma among health care providers was affected by mimicry of symptoms and lack of continuous education on asthma. Our study showed lack of Information Education and Communication (IEC) material and lack of use of bulk messages affected asthma awareness. Our study showed that clinical meetings on asthma, having asthma training manuals, (IEC) materials and guidelines for asthma diagnosis and management could improve health care providers' awareness of asthma. Bulk messages on asthma through network providers, social media and bill boards, commemorating world asthma day, edutainment, asthma ambassadors and multimedia were suggested as means of improving awareness of asthma among the public. CONCLUSION: We concluded that awareness of asthma can be improved using a framework. Such a framework ultimately improves the quality of asthma care.

Protocol on a systematic review of qualitative studies on asthma treatment challenges experienced in Sub-Saharan Africa.

BACKGROUND: Asthma is a major worldwide public health problem affecting an estimated 334 million people with over 300,000 deaths annually. Twenty-two million disability-adjusted life years (DALYs) are lost annually due to asthma. The condition may present many challenges if not managed well and effectively. This systematic review will provide a comprehensive synthesis of qualitative literature regarding the challenges experienced in the management of asthma and strategies adopted to counter these challenges. The review will answer the following questions: (i) what challenges have been experienced in the treatment of asthma in Sub-Saharan Africa (SSA)? and (ii) what strategies have been used to overcome asthma treatment challenges in SSA? METHODS: The reviewers will search for the following databases for relevant qualitative studies: PubMed/MEDLINE, Scopus/Embase (Elsevier), EbscoHost, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Google Scholar, using the Medical Subject Headings (MeSH) and controlled vocabulary. These articles must have been published in the English language between January 2008 and December 2018. The identified papers will then be assessed for meeting eligibility criteria. Two independent reviewers will screen titles and abstracts of articles and then review the full texts of the selected research articles. Standard data extraction forms will be utilised, and the quality of the included studies will be assessed using the Joanna Briggs checklist for qualitative research appraisal tool. Results from eligible articles will be qualitatively synthesised using the framework synthesis approach and reported according to the Enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement. DISCUSSION: This systematic review will provide an overview of reported challenges in the treatment of asthma in Sub-Saharan Africa from 2008 to 2018. The review is expected to provide information that will help form the basis for future research, policy development and practice in treatment of asthma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018095802.

Evidence of a distinct group of Black African patients with systemic lupus erythematosus.

BACKGROUND: The autoimmune disease systemic lupus erythematosus (SLE) occurs more frequently in patients of African descent with high morbidity and mortality. Current SLE diagnostic criteria including antinuclear antibody (ANA) reactivity are derived largely from non-African populations. This study characterises ANA reactivity patterns and relates them to SLE clinical presentation in Black African patients. METHODS: Sera from Black participants (61 patients with SLE and 100 controls) aged 1-81 years were analysed for reactivity against the antigens: uridine 1-ribonuclear protein, Smith uridine-1-5 ribonuclear protein antigen, soluble substance-A, recombinant Ro-52, soluble substance-B, Scl-70, cytoplasmic histidyl-tRNA synthetase antigen, proliferating cell nuclear antigen (PCNA), nucleosomes, ribonuclear P-protein, antimitochondrial antibody M2 (AMA-M2), histones, double-stranded DNA (dsDNA), centromere protein B and polymyositis-sclerosis overlap antigen. FINDINGS: A significantly higher proportion (97%) of the 61 patients with SLE had detectable autoantibody reactivity compared with 15% of the 100 controls (p<0.001). The highest frequencies of autoantibody reactivity in patients with SLE were against the dsDNA antigen (41%) and PCNA (54%). Anti-PCNA and anti-dsDNA reactivity were mutually exclusive (p<0.001) giving rise to two distinct groups of Black African patients with SLE. The first group (n=25) had reactivity profiles consistent with international standard SLE definitions, including anti-dsDNA reactivity, and was 13 times more likely to present with joint symptoms. The larger, second group (n=34), characterised by anti-PCNA and anti-AMA-M2 reactivity, was nine times more likely to present with only cutaneous symptoms. INTERPRETATION: Our study demonstrates a need to extend autoantibody panels to include anti-PCNA in the diagnostic process of Black African patients and further refine the predictive values of the reactivity to different antigens to differentiate SLE syndromes in African populations.

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.

Der p 11 is a major allergen for house dust mite-allergic patients suffering from atopic dermatitis.

House dust mites (HDMs) belong to the most potent indoor allergen sources worldwide and are associated with allergic manifestations in the respiratory tract and the skin. Here we studied the importance of the high-molecular-weight group 11 allergen from Dermatophagoides pteronyssinus (Der p 11) in HDM allergy. Sequence analysis showed that Der p 11 has high homology to paramyosins from mites, ticks, and other invertebrates. A synthetic gene coding for Der p 11 was expressed in Escherichia coli and rDer p 11 purified to homogeneity as folded, alpha-helical protein as determined by circular dichroism spectroscopy. Using antibodies raised against rDer p 11 and immunogold electron microscopy, the allergen was localized in the muscle beneath the skin of mite bodies but not in feces. IgE reactivity of rDer p 11 was tested with sera from HDM-allergic patients from Europe and Africa in radioallergosorbent test-based dot-blot assays. Interestingly, we found that Der p 11 is a major allergen for patients suffering from atopic dermatitis (AD), whereas it is only a minor allergen for patients suffering from respiratory forms of HDM allergy. Thus, rDer p 11 might be a useful serological marker allergen for the identification of a subgroup of HDM-allergic patients suffering from HDM-associated AD.

The genetic predisposition to produce high levels of TGF-beta1 impacts on the severity of eclampsia/pre-eclampsia.

OBJECTIVES: To investigate the hypothesis that women who are genetically programmed to produce higher levels of transforming growth factor-beta 1 are more likely to develop severe eclampsia/pre-eclampsia. DESIGN: Case-control study. METHODS: Blood samples from women whose pregnancy was complicated by eclampsia (n=37) or pre-eclampsia (n=49) and healthy controls (n=86) were analyzed for the presence of polymorphisms at codons 10 and 25 of the transforming growth factor-beta 1 gene. The polymorphisms are thought to determine whether an individual produces low, medium, or high levels of the cytokine. The analysis was carried out using the ARMS-PCR technique. RESULTS: Women who developed eclampsia/pre-eclampsia with severe renal and neurological complications or had neonatal deaths/still births were more likely to have the high-producer allele T in codon 10 of the transforming growth factor-beta 1 gene than healthy controls. By contrast, the transforming growth factor-beta 1 producer genotype and allele frequency as determined by gene polymorphisms at codon 25 were comparable in cases and controls. The cytokine producer status per se appears to had no bearing on whether a patient developed eclampsia/pre-eclampsia. CONCLUSIONS: Our findings suggest that women who experience eclampsia/pre-eclampsia with severe maternal and/or fetal complications are more likely to have a genetic predisposition to produce high levels of transforming growth factor-beta 1 as defined by polymorphisms at codon 10. While it is recognized that eclampsia/pre-eclampsia has heterogenous pathomechanisms, we have demonstrated a strong relationship between poor maternal and pregnancy outcomes and codon 10 polymorphisms. The characterization of the immunogenetic make-up of the women may be an additional tool in the differentiation of component pathologies and/or prediction of severity of the syndrome.

Detection of human papillomavirus in urine and cervical swabs from patients with invasive cervical cancer.

Despite the high prevalence of both human papillomavirus (HPV) infections and cervical cancer among Zimbabwean women, the ability to test for HPV infection of the uterine cervix is limited by a lack of an easy sample collection method that does not require gynecological examination. The presence of HPVs in urine and cervical swab samples collected from 43 women who presented with invasive cervical cancer was investigated. HPV detection was done by means of degenerate primers in a nested polymerase chain reaction (PCR). Typing of HPVs was done using restriction fragment length polymorphism (RFLP) analysis. HPV was identified and typed in 98% (42/43) of cervical swabs and 72% (31/43) of paired urine samples. HPV type 16 was the most common (25/42, 59%), followed by types: 33 (13/42, 31%), 18 (6/42, 14%), and 31 (1/42, 2%). Type-specific concordance between cervical and urine samples was high (22/28, 79%). Therefore, the HPV types identified in urine samples in most cases represent the same HPV type infecting the cervical epithelium. The results suggest that urine may be a practical sample for testing of HPV urogenital infection. Further research is required before the detection of HPV in urine can be applied in the routine cervical screening programs.