Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.).

Psychological distress among healthcare workers accessing occupational health services during the COVID-19 pandemic in Zimbabwe.

BACKGROUND: Healthcare workers (HCWs) have experienced anxiety and psychological distress during the COVID-19 pandemic. We established and report findings from an occupational health programme for HCWs in Zimbabwe that offered screening for SARS-CoV-2 with integrated screening for comorbidities including common mental disorder (CMD) and referral for counselling. METHODS: Quantitative outcomes were fearfulness about COVID-19, the Shona Symptom Questionnaire (SSQ-14) score (cutpoint 8/14) and the number and proportion of HCWs offered referral for counselling, accepting referral and counselled. We used chi square tests to identify factors associated with fearfulness, and logistic regression was used to model the association of fearfulness with wave, adjusting for variables identified using a DAG. Qualitative data included 18 in-depth interviews, two workshops conducted with HCWs and written feedback from counsellors, analysed concurrently with data collection using thematic analysis. RESULTS: Between 27 July 2020-31 July 2021, spanning three SARS-CoV-2 waves, the occupational health programme was accessed by 3577 HCWs from 22 facilities. The median age was 37 (IQR 30-43) years, 81.9% were women, 41.7% said they felt fearful about COVID-19 and 12.1% had an SSQ-14 score ≥ 8. A total of 501 HCWs were offered referral for counselling, 78.4% accepted and 68.9% had ≥1 counselling session. Adjusting for setting and role, wave 2 was associated with increased fearfulness over wave 1 (OR = 1.26, 95% CI 1.00-1.60). Qualitative data showed high levels of anxiety, psychosomatic symptoms and burnout related to the pandemic. Mental wellbeing was affected by financial insecurity, unmet physical health needs and inability to provide quality care within a fragile health system. CONCLUSIONS: HCWs in Zimbabwe experience a high burden of mental health symptoms, intensified by the COVID-19 pandemic. Sustainable mental health interventions must be multisectoral addressing mental, physical and financial wellbeing.

The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial.

BACKGROUND: Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF). METHODS: We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing. RESULTS: The participants' median (interquartile range (IQR)) age was 18.1 (IQR: 15.1-20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146). CONCLUSION: A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART. TRIAL REGISTRATION: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441.

Diagnostic Accuracy of Pan-Degenerate Amplification and Adaptation Assay for HIV-1 Drug Resistance Mutation Analysis in Low- and Middle-Income Countries.

HIV drug resistance (HIVDR) is a barrier to sustained virologic suppression in low- and middle-income countries (LMICs). Point mutation assays targeting priority drug resistance mutations (DRMs) are being evaluated to improve access to HIVDR testing. In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS). Plasma samples from adolescents and young adults (aged 10 to 24 years) failing antiretroviral therapy (viral load, >1,000 copies/ml on 2 consecutive occasions 1 month apart) were analyzed. Sensitivity and specificity of the PANDAA assay were determined by a proprietary application designed by Aldatu Biosciences. Agreement between genotyping methods was evaluated using Cohen's kappa coefficient. One hundred fifty samples previously characterized by Sanger sequencing were evaluated using PANDAA. For all DRMs detected, PANDAA showed a sensitivity and specificity of 98% and 94%, respectively. For nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 98% (95% confidence interval [CI], 92% to 100%) and 100% (94% to 100%), respectively. For non-nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 100% (97% to 100%) and 76% (61% to 87%), respectively. PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720). Of the 21 false-positive samples genotyped by PANDAA, only 6 (29%) were identified as low-abundance variants by NGS. With the high sensitivity and specificity to detect major DRMs, PANDAA could represent a simple and rapid alternative HIVDR assay in LMICs.

Tenofovir-associated kidney disease in Africans: a systematic review.

BACKGROUND: Data on chronic kidney disease development in HIV infection is important towards building a comprehensive knowledge of HIV, ageing and polypharmacy in Africa. Several previous studies on tenofovir-associated kidney disease in Africa have shown conflicting results. This review summarises what is known about the development of kidney disease in HIV-positive African patients on tenofovir disoproxil fumarate (TDF)-containing ART. We set out to document the occurrence of kidney disease in HIV-positive Africans on TDF-containing ART in population-based studies and to evaluate the renal safety of TDF in Africans. METHODS: We conducted a systemic review using published studies which were identified through a computerized search of original research using the Medline/PubMed database, EMBASE, EBM Reviews, Proquest Google Scholar and Global Health reported from inception until 5 October 2017. Two reviewers independently abstracted the data and performed quality assessment of the included studies. We screened 595 articles and included 31 in the qualitative analysis performed. RESULTS: A total of 106 406 patients (of whom 66,681 were on Tenofovir) were involved in these 31 studies with sample sizes ranging from 30 to 62,230. Duration on tenofovir-containing ART ranged from those initiating ART at baseline to those who received TDF for up to 9 years. All but one of the studies involved only patients 16 years and older. The studies had differing definitions of kidney dysfunction and were of variable study design quality. The documented outcomes had substantial discrepancies across the studies, most likely due to methodological differences, study size and disparate outcome definitions. CONCLUSIONS: Our review identified studies in Africans reporting statistically significant renal function decline associated with TDF use but the clinical significance of this effect was not enough to contraindicate its continued use in ART regimens. Consistent with studies in other populations, patients are at greater risk if they have pre-existing renal disease and are more advanced in age. More research is needed on paediatric populations under 16 years of age. Trial registration This review was registered on Prospero (registration number CRD42018078717).

A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots.

Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93; P < 0.0001). The mean difference between DBS and plasma VL values was -1.06 log10 copies/ml (95% confidence interval [CI], -1.17, -0.97; P < 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system.

Virological, weight, and drug resistance outcomes among patients initiating a dolutegravir-based first-line antiretroviral therapy regimen in Zimbabwe.

OBJECTIVE: Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up in Africa. However, clinical experience with DTG and patterns of HIV drug resistance (HIVDR) are sparse in Zimbabwe. We assessed virological, weight, and HIVDR outcomes among individuals initiating on a DTG-based ART. DESIGN: We conducted a prospective cohort study among HIV-infected adult (≥18 years old) individuals attending care at Parirenyatwa hospital, Harare, Zimbabwe between October 2021 and April 2023. METHODS: Viral load and weight were assessed at both baseline and follow-up (≥24weeks) visits. HIVDR genotyping was performed by Sanger sequencing among participants with virological failure (viral load ≥1000 copies/ml) at follow-up visit. Factors associated with weight gain were determined using logistic regression analysis on STATA 17.0. RESULTS: One hundred and seventy-two participants were enrolled in the study. The median [interquartile range (IQR) age was 39 (29-48)] years whilst the median (IQR) CD4 + cell count and log 10 viral load at enrolment was 175 (58-328) cells/µl and 5.41 (4.80-5.74), respectively. After a median (IQR) duration of 27 (25-30) weeks on DTG, of the 131 participants with follow-up viral load data available, 129 (98%) had viral load less than 1000 copies/ml and among the 2 (2%) participants with viral load at least 1000 copies/ml, no emergent HIVDR was detected. We observed a significant increase in weight among the participants. The average weight gain was 5.25 kgs ( P  < 0.0001). Baseline CD4 + cell count at least 200 cells/µl was significantly associated with at a smaller weight gain [odds ratio (OR) = 0.26; 95% confidence interval (CI) 0.12-0.58, P  = 0.001]. CONCLUSION: We found high virological suppression and an increased weight among people initiating on DTG in a resource-limited setting. Encouragingly, HIVDR to DTG remains rare.

Prevalence of chronic conditions and multimorbidity among healthcare workers in Zimbabwe: Results from a screening intervention.

The burden of non-communicable diseases (NCDs) in southern Africa is expanding and is superimposed on high HIV prevalence. Healthcare workers are a scarce resource; yet are vital to health systems. There are very limited studies on the burden of chronic conditions among healthcare workers in Africa, and none exploring multimorbidity (≥2 chronic conditions). We describe the epidemiology of infectious (HIV) and non-communicable chronic conditions, and multimorbidity, among Zimbabwean healthcare workers. Healthcare workers (≥18 years) in eight Zimbabwean provinces were invited to a voluntary, cross-sectional health-check, including HIV, diabetes, hypertension and mental health screening. Statistical analyses described the prevalence and risk factors for multimorbidity (two or more of HIV, diabetes, hypertension or common mental disorder) and each condition. Missing data were handled using multiple imputation. Among 6598 healthcare workers (July 2020-July 2022) participating in the health-check, median age was 37 years (interquartile range 29-44), 79% were women and 10% knew they were living with HIV. Half had at least one chronic condition: 11% were living with HIV, 36% had elevated blood pressure, 12% had elevated HbA1c and 11% had symptoms of common mental disorder. The overall prevalence of multimorbidity was 15% (95% CI: 13-17%); 39% (95% CI: 36-43%) among people aged 50 and older. Whilst most HIV was diagnosed and treated, other chronic conditions were usually undiagnosed or uncontrolled. Limiting our definition of multimorbidity to two or more screened conditions sought to reduce bias due to access to diagnosis, however, may have led to a lower reported prevalence than that found using a wider definition. Half of healthcare workers screened were living with a chronic condition; one in seven had multimorbidity. Other than HIV, most conditions were undiagnosed or untreated. Multisectoral action to implement contextually relevant, chronic disease services in Africa is urgently needed. Specific attention on health workers is required to protect and retain this critical workforce.

Evaluation of a comprehensive health check offered to frontline health workers in Zimbabwe.

Health workers are essential for a functioning healthcare system, and their own health is often not addressed. During the COVID-19 pandemic health workers were at high risk of SARS-CoV-2 infection whilst coping with increased healthcare demand. Here we report the development, implementation, and uptake of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases for health workers in Zimbabwe during the COVID-19 pandemic. Health checks were offered to health workers in public and private health facilities from July 2020 to June 2022. Data on the number of health workers accessing the service and yield of screening was collected. Workshops and in-depth interviews were conducted to explore the perceptions and experiences of clients and service providers. 6598 health workers across 48 health facilities accessed the service. Among those reached, 5215 (79%) were women, the median age was 37 (IQR: 29-44) years and the largest proportion were nurses (n = 2092, 32%). 149 (2.3%) healthcare workers tested positive for SARS-CoV-2. Uptake of screening services was almost 100% for all screened conditions except HIV. The most common conditions detected through screening were elevated blood pressure (n = 1249; 19%), elevated HbA1c (n = 428; 7.7%) and common mental disorder (n = 645; 9.8%). Process evaluation showed high acceptability of the service. Key enablers for health workers accessing the service included free and comprehensive service provision, and availability of reliable point-of-care screening methods. Implementation of a comprehensive health check for health workers was feasible, acceptable, and effective, even during a pandemic. Conventional occupational health programmes focus on infectious diseases. In a society where even health workers cannot afford health care, free comprehensive occupational health services may address unmet needs in prevention, diagnosis, and treatment for chronic non-communicable conditions.

Low Prevalence of Pre-Treatment and Acquired Drug Resistance to Dolutegravir among Treatment Naïve Individuals Initiating on Tenofovir, Lamivudine and Dolutegravir in Zimbabwe.

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29-48) years and 5.41 (4.80-5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25-30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.

Effects of Gender and Baseline CD4 Count on Post-Treatment CD4 Count Recovery and Outcomes in Patients with Advanced HIV Disease: A Retrospective Cohort Study.

Presentation to care with advanced HIV disease (AHD) is a significant problem in sub-Saharan Africa. We evaluated factors associated with immune recovery among individuals presenting to care with AHD in Zimbabwe. We conducted a retrospective evaluation of outcomes among adult (>18 years old) individuals with AHD (CD4 count ≤200 cells/mm3) receiving care at 18 outpatient primary care clinics in Harare, Zimbabwe. Baseline and 12-month CD4 count data were extracted from medical records. CD4 count recovery (defined as CD4 count >200 cells/mm3) after 12 months on non-nucleotide reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) regimen was determined and factors associated with CD4 count recovery were established using logistic regression. All statistical analysis was performed on SPSS v23. A total of 1,338 participant records were included in the analysis. The median interquartile range (IQR) age was 37 (30-43) years and 52% were females. The baseline median (IQR) CD4 count was 50 (28-75) cells/mm3 and was significantly lower among patients with history of cryptococcal meningitis compared to those without [25 (10-52) vs. 52 (32-77), respectively; p = .0009]. The median (IQR) CD4 count at 12 months after ART initiation increased from 50 (28-75) at baseline to 180 (92-290) cells/mm3. Immune recovery with a CD4 count >200 cells/mm3 was observed in 181/417 (43%). Male gender and low baseline CD4 count were strong predictors of poor immunological recovery on ART. Immunological recovery following ART initiation was 43% among individuals with AHD. Male patients are most vulnerable to persistent immunological failure. Clinical Trial Registration number: NCT02434172.

Factors associated with CD4 + cell count recovery among males and females with advanced HIV disease.

OBJECTIVE: HIV/AIDS mortality remains significantly high in sub-Saharan Africa, mostly driven by opportunistic infections and advanced HIV disease (AHD). This study aimed to assess CD4 + cell count recovery following ART initiation and factors associated with immune reconstitution. METHODS: We conducted a prospective cohort study between 2015 and 2016. HIV-infected adults (≥18 years) with AHD (CD4 + cell count ≤100 cells/µl) receiving care at 20 outpatient HIV treatment facilities in Harare, Zimbabwe were enrolled. CD4 + cell count recovery (CD4 + cell count >200 cells/µl) was assessed following 12-month ART initiation and factors associated with immune reconstitution were investigated using logistic regression analysis. All statistical analyses were performed on Statistical Package for the Social Sciences (SPSS) version 23. RESULTS: 1320 participants were enrolled and 56.4% were males. The median (interquartile range, IQR) age was 37 (32-43) years. Tuberculosis was seen in 16.0%. Of the 739 participants that had CD4 + cell count at 12 months, CD4 + cell count recovery above 200 cells/µl was observed in 163 (22.1%) participants. Median (IQR) CD4 + cell count at 12-months increased to 127 (75-190) cells/µl from 31 (14-55) at baseline. Factors associated with CD4 + cell count recovery were younger age at baseline [odds ratio (OR) ≥40/<40  = 0.58, 95% confidence interval (CI): 0.40-0.85, P  = 0.005), sex (OR female/male  = 2.07, 95% CI: 1.44-2.99, P  < 0.0001) and baseline CD4 + cell count (OR ≥50/<50  = 1.60, 95% CI: 1.10-2.33, P  = 0.013). CONCLUSION: A significant proportion (77.9%) of patients seeking care with AHD in a resource limited setting failed to recover a CD4 + cell count >200 cells/µl. Male sex, older age and low CD4 + cell count at ART initiation were factors associated with poor immune reconstitution. Better differentiated care deliveries targeting this vulnerable population are critical for improving clinical outcomes and quality of life of the patients.

Investigating Attitudes, Motivations and Key Influencers for COVID-19 Vaccination Uptake among Late Adopters in Urban Zimbabwe.

The rapid development of vaccines in response to the COVID-19 pandemic has provided an effective tool for the management of COVID-19. However, in many African countries there has been a poor uptake of COVID-19 vaccines with only 32.5% first vaccine dose coverage compared to the WHO global target of 70%. As vaccine access improves, one of the important drivers of low uptake has been vaccine hesitancy, driven by levels of confidence, convenience, and complacency. Between 4 January-11 February 2022, we conducted a survey of vaccine late adopters to assess factors that influenced adults in Harare, Zimbabwe to present for their first COVID-19 vaccine dose almost 12 months after the vaccination program began. Of the 1016 adults enrolled, 50% were female and 12.4% had HIV co-infection. Binary logistic regression models were developed to understand factors associated with vaccine confidence. Women were more likely to have negative views about the COVID-19 vaccine compared to men (OR 1.51 (95%CI 1.16, 1.97, p = 0.002). Older adults (≥40 years) compared with youth (18-25 years) were more likely to have 'major concerns' about vaccines. When asked about their concerns, 602 (59.3%) considered immediate side effects as a major concern and 520 (52.1%) were concerned about long-term health effects. People living with HIV (PLWH) were more likely to perceive vaccines as safe (OR 1.71 (95%CI: 1.07, 2.74, p = 0.025) and effective (1.68 (95%CI: 1.07, 2.64, p = 0.026). Internet users were less likely to perceive vaccines as safe (OR 0.72 (95% CI: 0.55, 0.95, p = 0.021) compared to non-Internet users; and social media was a more likely source of information for youth and those with higher education. Family members were the primary key influencers for 560 (55.2%) participants. The most important reason for receiving the COVID-19 vaccine for 715 (70.4%) participants was the protection of individual health. Improving vaccine coverage will need targeted communication strategies that address negative perceptions of vaccines and associated safety and effectiveness concerns. Leveraging normative behavior as a social motivator for vaccination will be important, as close social networks are key influences of vaccination.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centers for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 2905 healthcare workers employed at 37 facilities who participated in the study, 2818 (97%, 95% CI [92%-102%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centres for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 3,086 healthcare workers employed at 43 facilities who participated in the study, 2,986 (97%, 95% CI [92%-100%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.

Chronic lung disease in adolescents with delayed diagnosis of vertically acquired HIV infection.

BACKGROUND: Long-term survivors of vertically acquired human immunodeficiency virus (HIV) infection are reaching adolescence in large numbers in Africa and are at high risk of delayed diagnosis and chronic complications of untreated HIV infection. Chronic respiratory symptoms are more common than would be anticipated based on the HIV literature. METHODS: Consecutive adolescents with presumed vertically acquired HIV attending 2 HIV care clinics in Harare, Zimbabwe, were recruited and assessed with clinical history and examination, CD4 count, pulmonary function tests, Doppler echocardiography, and chest radiography (CXR). Those with suspected nontuberculous chronic lung disease (CLD) were scanned using high-resolution computed tomography (HRCT). RESULTS: Of 116 participants (43% male; mean age, 14 ± 2.6 years, mean age at HIV diagnosis, 12 years), 69% were receiving antiretroviral therapy. Chronic cough and reduced exercise tolerance were reported by 66% and 21% of participants, respectively; 41% reported multiple respiratory tract infections in the previous year, and 10% were clubbed. More than 40% had hypoxemia at rest (13%) or on exercise (29%), with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) in 7%. Forced expiratory volume in 1 second (FEV(1)) was <80% predicted in 45%, and 47% had subtle CXR abnormalities. The predominant HRCT pattern was decreased attenuation as part of a mosaic attenuation pattern (31 of 56 [55%]), consistent with small airway disease and associated with bronchiectasis (Spearman correlation coefficient (r(2) = 0.8) and reduced FEV(1) (r(2) = -0.26). CONCLUSIONS: Long-term survivors of vertically acquired HIV in Africa are at high risk of a previously undescribed small airway disease, with >40% of unselected adolescent clinic attendees meeting criteria for severe hypoxic CLD. This condition is not obvious at rest. Etiology, prognosis, and response to treatment are currently unknown.

Diagnostic Accuracy of Point of Care Cryptococcal Antigen Lateral Flow Assay in Fingerprick Whole Blood and Urine Samples for the Detection of Asymptomatic Cryptococcal Disease in Patients with Advanced HIV Disease.

Cryptococcal disease (CD) is a leading cause of mortality among individuals with advanced HIV disease (AHD). Screening with serum cryptococcal antigen (sCrAg) lateral flow assay (LFA) enables early detection of subclinical disease but requires venipuncture and laboratory processing. Clinic-based point of care (POC) CrAg screening tests using urine or fingerprick whole blood could facilitate early diagnosis of CD. We evaluated the diagnostic performance of POC clinic-based fingerprick whole blood and urine CrAg compared to the gold standard laboratory sCrAg LFA in screening for CD among asymptomatic individuals with CD4 counts of <200 cells/µL in Harare, Zimbabwe. sCrAg positive participants who consented to a lumbar puncture also had cerebrospinal fluid (CSF) CrAg testing and titers for CSF-positive specimens. A total of 1,333 individuals were screened, and over half (56.6%) were males. The median (interquartile range) CD4 count was 27.5 (11-46) cells/µL. We found a sensitivity of 63.8% (95% CI: 54.8-72.1) and specificity of 84.0% (95% CI: 81.7-86.0) for urine CrAg, and a sensitivity of 48.0% (95% CI: 39.1-57.1) and specificity of 99.5% (95% CI: 98.9-99.8) was found for fingerprick whole blood. The sensitivity of both POC CrAg tests increased in individuals with sCrAg titers of ≥1:160, CD4 count of <50 cells/µL and disseminated central nervous system (CNS) disease. Clinic-based POC urine and fingerprick whole blood CrAg testing performed better in screening for CD among AHD patients with CNS disease. More sensitive assays to identify AHD patients with asymptomatic CD are needed. IMPORTANCE Cryptococcal disease (CD) remains a leading cause of morbidity and mortality among individuals with advanced HIV disease (AHD). Identifying point of care (POC) approaches to screening for CD in asymptomatic individuals is important to guide therapeutic management. We evaluated the use of POC fingerprick whole blood and urine testing for cryptococcal disease in patients with AHD as compared with laboratory-based serum antigen testing. POC fingerprick whole blood and urine testing had low sensitivity and specificity in asymptomatic individuals with AHD. Most analysis has focused on evaluating test performance in symptomatic individuals. Here we show that POC testing with whole blood and urine samples should not be used to screen for asymptomatic CD in AHD.

Attitudes to Vaccine Mandates among Late Adopters of COVID-19 Vaccines in Zimbabwe.

Despite sufficient supply, <25% of the population in sub-Saharan Africa has received at least one dose of COVID-19 vaccine. Vaccine mandates have previously been effective in increasing vaccine uptake. Attitudes to COVID-19 vaccine mandates and vaccines for children in African populations are not well understood. We surveyed late-adopters presenting for COVID-19 vaccination one year after program initiation in Zimbabwe. Logistic regression models were developed to evaluate factors associated with attitudes to mandates. In total, 1016 adults were enrolled; 690 (67.9%) approved of mandating vaccination for use of public spaces, 686 (67.5%) approved of employer mandates, and 796 (78.3%) approved of mandating COVID-19 vaccines for schools. Individuals of lower economic status were twice as likely as high-income individuals to approve of mandates. Further, 743 (73.1%) participants indicated that they were extremely/very likely to accept vaccines for children. Approval of vaccine mandates was strongly associated with perceptions of vaccine safety, effectiveness, and trust in regulatory processes that approved vaccines. Vaccine hesitancy is an important driver of low vaccine coverage in Africa and can be mitigated by vaccine mandates. Overall, participants favored vaccine mandates; however, attitudes to mandates were strongly associated with level of education and socioeconomic status.

Vaccine Adverse Events Following COVID-19 Vaccination with Inactivated Vaccines in Zimbabwe.

Vaccination is one of the most effective methods for preventing morbidity and mortality from COVID-19. Vaccine hesitancy has led to a decrease in vaccine uptake; driven by misinformation, fear, and misperceptions of vaccine safety. Whole inactivated vaccines have been used in one-fifth of the vaccine recipients in Africa, however there are limited real-world data on their safety. We evaluated the reported adverse events and factors associated with reported adverse events following vaccination with whole inactivated COVID-19 vaccines-BBiBP-CorV (Sinopharm) and CoronaVac (Sinovac). A quantitative survey evaluating attitudes and adverse events from vaccination was administered to 1016 adults presenting at vaccination centers. Two follow-up telephone interviews were conducted to determine adverse events after the first and second vaccination dose. Overall, the vaccine was well tolerated; 26.0% and 14.4% reported adverse events after the first and second dose, respectively. The most frequent local and systemic adverse events were pain at the injection site and headaches, respectively. Most symptoms were mild, and no participants required hospitalization. Participants who perceived COVID-19 vaccines as safe or had a personal COVID-19 experience were significantly less likely to report adverse events. Our findings provide data on the safety and tolerability of whole inactivated COVID-19 vaccines in an African population, providing the necessary data to create effective strategies to increase vaccination and support vaccination campaigns.