Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

Primary headache disorders among people living with HIV in Lusaka, Zambia.

OBJECTIVE: We completed a cross-sectional survey study to determine headache prevalence and its association with HIV characteristics among people living with HIV (PLHIV) in Lusaka, Zambia. BACKGROUND: Headaches are common but their association with HIV status is unknown. METHODS: The HARDSHIP survey, a headache epidemiology questionnaire previously validated in Zambia, was distributed during a 3-month period to 3666 consecutive adult PLHIV attending routine clinic appointments at the Adult Infectious Diseases Centre at the University Teaching Hospital in Lusaka, Zambia. HIV disease characteristics were abstracted from their charts. RESULTS: 1015 (27.7%) participants responded to the survey. Adjusted for age, 64% reported having a headache within the last year unrelated to another illness. Among participants, 201 met criteria for migraine (20%), 259 for tension-type headache (26%), 18 for probable medication-overuse headache (2%), and 121 for undetermined headache (12%). Prevalence for tension-type headache was significantly higher than that of migraine (P < 0.001). After adjusting for age and sex, higher CD4 counts were associated with migraine. No other associations were observed between overall headache or headache type with HIV disease characteristics including CD4 count, viral load, antiretroviral regimen, and time since HIV diagnosis. CONCLUSIONS: Headaches are highly prevalent among this cohort of PLHIV in Zambia. Optimizing headache treatment and integrating it into routine HIV care may improve quality of life for a substantial proportion of PLHIV in Zambia.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022.

OBJECTIVES: The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, 'What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?' DESIGN/SETTING: We conducted a test-negative case-control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022. PARTICIPANTS: 1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product. RESULTS: We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26-38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56-144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: -7.0% to 63.3%) during the Omicron period. CONCLUSIONS: COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Why local antibiotic resistance data matters - Informing empiric prescribing through local data collation, app design and engagement in Zambia.

BACKGROUND: Control of antimicrobial resistance (AMR) relies on local knowledge and local intervention implementation. Effective antibiotic stewardship requires locally-suitable prescribing guidelines. We aimed to use a novel digital tool (the ZARIApp) and a participatory approach to help develop locally-relevant empiric antibiotic prescribing guidelines for two hospitals in Lusaka, Zambia. METHODS: We produced an AMR report using samples collected locally and routinely from adults within the prior two years (April 2020 - April 2022). We developed the ZARIApp, which provides prescribing recommendations based on local resistance data and antibiotic prescribing practices. We used qualitative evaluation of focus group discussions among healthcare professionals to assess the feasibility and acceptability of using the ZARIApp and identify the barriers to and enablers of this stewardship approach. RESULTS: Resistance prevalence was high for many key pathogens: for example, 73% of 41 Escherichia coli isolates were resistant to ceftriaxone. We identified that high resistance rates were likely due to low levels of requesting and processing of microbiology samples from patients leading to insufficient and unrepresentative microbiology data. This emerged as the major barrier to generating locally-relevant guidelines. Through active stakeholder engagement, we modified the ZARIApp to better support users to generate empirical antibiotic guidelines within this context of unrepresentative microbiology data. Qualitative evaluation of focus group discussions suggested that the resulting ZARIApp was useful and easy to use. New antibiotic guidelines for key syndromes are now in place in the two study hospitals, but these have substantial residual uncertainty. CONCLUSIONS: Tools such as the free online ZARIApp can empower local settings to better understand and optimise how sampling and prescribing can help to improve patient care and reduce future AMR. However, the usability of the ZARIApp is severely limited by unrepresentative microbiology data; improved routine microbiology surveillance is vitally needed.

The UTH-UMB Global Health Education Collaboration: Building a Bidirectional Exchange Based on Equity and Reciprocity.

The global health exchange program between the University Teaching Hospitals (UTH) of Lusaka, Zambia and the University of Maryland, Baltimore (UMB) has been operating since 2015. As trainees and facilitators of this exchange program, we describe our experiences working in Lusaka and Baltimore, and strengths and challenges of the partnership. Since 2015, we have facilitated rotations for 71 UMB trainees, who spent four weeks on the Infectious Disease (ID) team at UTH. Since 2019 with funding from UMB, nine UTH ID trainee physicians spent up to six weeks each rotating on various ID consult services at University of Maryland Medical Center (UMMC). Challenges in global health rotations can include inadequate preparation or inappropriate expectations among high-income country trainees, low-value experiences for low- and middle-income country trainees, lack of appropriate mentorship at sites, and power imbalances in research collaborations. We try to mitigate these issues by ensuring pre-departure and on-site orientation for UMB trainees, cross-cultural mentored experiences for all trainees, and intentional sharing of authorship and credit on scientific collaborations. We present a description of our medical education collaboration as a successful model for building equitable and reciprocal collaborations between low- and middle-income countries and high-income countries, and offer suggestions for future program initiatives to enhance global health education equity among participants and organizations.

Hypertension among persons living with HIV-Zambia, 2021; A cross-sectional study of a national electronic health record system.

Hypertension is a major risk factor for cardiovascular disease, which is a common cause of death in Zambia. Data on hypertension prevalence in Zambia are scarce and limited to specific geographic areas and/or populations. We measured hypertension prevalence among persons living with HIV (PLHIV) in Zambia using a national electronic health record (EHR) system. We did a cross-sectional study of hypertension prevalence among PLHIV aged ≥18 years during 2021. Data were extracted from the SmartCare EHR, which covers ~90% of PLHIV on treatment in Zambia. PLHIV with ≥2 clinical visits in 2021 were included. Hypertension was defined as ≥2 elevated blood pressure readings (systolic ≥140 mmHg/diastolic ≥90 mmHg) during 2021 and/or on anti-hypertensive medication recorded in their EHR ≤5 years. Logistic regression was used to assess for associations between hypertension and demographic characteristics. Among 750,098 PLHIV aged ≥18 years with ≥2 visits during 2021, 101,363 (13.5%) had ≥2 recorded blood pressure readings. Among these PLHIV, 14.7% (95% confidence interval [CI]: 14.5-14.9) had hypertension. Only 8.9% of PLHIV with hypertension had an anti-hypertensive medication recorded in their EHR. The odds of hypertension were greater in older age groups compared to PLHIV aged 18-29 years (adjusted odds ratio [aOR] for 30-44 years: 2.6 [95% CI: 2.4-2.9]; aOR for 45-49 years: 6.4 [95% CI: 5.8-7.0]; aOR for ≥60 years: 14.5 [95% CI: 13.1-16.1]), urban areas (aOR: 1.9 [95% CI: 1.8-2.1]), and on ART for ≥6-month at a time (aOR: 1.1 [95% CI: 1.0-1.2]). Hypertension was common among PLHIV in Zambia, with few having documentation of treatment. Most PLHIV were excluded from the analysis because of missing BP measurements. Strengthening integrated management of non-communicable diseases in HIV clinics might help to diagnose and treat hypertension in Zambia. Addressing missing data of routine clinical data (like blood pressure) could improve non-communicable diseases surveillance in Zambia.

Mortality associated with third-generation cephalosporin resistance in Enterobacterales bloodstream infections at eight sub-Saharan African hospitals (MBIRA): a prospective cohort study.

BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.

A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings.

BACKGROUND: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19. METHODS: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences. RESULTS: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more ß-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001). CONCLUSIONS: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.

Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Phenotypic and genotypic antibiotic susceptibility profiles of Gram-negative bacteria isolated from bloodstream infections at a referral hospital, Lusaka, Zambia.

Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

Impact of the COVID-19 Pandemic on Tuberculosis Testing and Treatment at a Tertiary Hospital in Zambia.

Globally, tuberculosis (TB) testing and treatment have declined dramatically during the COVID-19 pandemic. We quantified the change in TB visits, testing, and treatment compared with a 12-month pre-pandemic baseline at the national referral hospital's TB Clinic in Lusaka, Zambia, in the first year of the pandemic. We stratified the results into early and later pandemic periods. In the first 2 months of the pandemic, the mean number of monthly TB clinic visits, prescriptions, and positive TB polymerase chain reaction (PCR) tests decreased as follow: -94.1% (95% CI: -119.4 to -68.8%), -71.4% (95% CI: -80.4 to -62.4%), and -73% (95% CI: -95.5 to -51.3%), respectively. TB testing and treatment counts rebounded in the subsequent 10 months, although the number of prescriptions and TB-PCR tests performed remained significantly lower than pre-pandemic. The COVID-19 pandemic significantly disrupted TB care in Zambia, which could have long-lasting impacts on TB transmission and mortality. Future pandemic preparedness planning should incorporate strategies developed over the course of this pandemic to safeguard consistent, comprehensive TB care.

Effects of the ECHO tele-mentoring program on HIV/TB service delivery in health facilities in Zambia: a mixed-methods, retrospective program evaluation.

BACKGROUND: In the quest to ensure that quality healthcare is provided to all citizens through building healthcare worker capacity and extending reach for expert services, Zambia's Ministry of Health (MoH) in collaboration with its partners PEPFAR through the CDC and HRSA, began to implement the Extension for Community Healthcare Outcomes (ECHO) tele-mentoring program across the country through the Health Workers for the 21st Century (HW21) Project and University Teaching Hospital HIV/AIDS Project (UTH-HAP). This ECHO tele-mentoring approach was deemed pivotal in helping to improve the human immunodeficiency virus (HIV) service delivery capacity of health care workers. METHOD: The study used a mixed method, retrospective program evaluation to examine ECHO participants' performance in the management of HIV/AIDS patients in all the 10 provinces of Zambia. CASE PRESENTATION: A phenomenological design was applied in order to elicit common experiences of ECHO users through focus group discussions using semi-structured facilitation guides in four provinces (Eastern, Lusaka, Southern and Western) implementing ECHO tele-mentoring approach. These provinces were purposively selected for this study. From which, only participants that had a monthly frequency of ECHO attendance of ten (10) and above were selected. The participants were purposively selected based on the type of cadre as well as facility type so that the final sample consisted of Doctors, Nurses, Midwives, Clinical Officers, Medical Licentiates, Pharmacy and Laboratory Personnel. All sessions were audio recorded and transcribed by the data collectors. A thematic content analysis approach was adopted for analyzing content of the interview's transcripts. RESULTS: Enhanced knowledge and skills of participants on HIV/TB improved by 46/70 (65.7%) in all provinces, while 47/70 (67.1%) of the participants reported that ECHO improved their clinical practice. Further, 12/70 (17.1%) of participants in all provinces reported that presenter/presentation characteristics facilitated ECHO implementation and participation. While, 15/70(21.4%) of the participants reported that ownership of the program had contributed to ECHO implementation and participation. Coordination, another enabler accounted for 14/70 (20%). Inclusiveness was reported as a barrier by 16/70 (22.8%) of the participants while 6/70 (8.6%) of them reported attitudes as a barrier (8.6%) to ECHO participation. In addition, 34/70 (48.6%) reported poor connectivity as a barrier to ECHO implementation and participation while 8/70 (11.5%) of the participants reported that the lack of ownership of the ECHO program was a barrier. 22/70 (31.4%) reported that increased workload was also a barrier to the program's implementation. CONCLUSION: Consistent with its logical pathway model, healthcare providers' participation in ECHO sessions and onsite mentorship contributed to improved knowledge on HIV/TB among health care providers and patient health outcomes. In addition, barriers to ECHO implementation were intrinsic to the program its self, such as coordination, presenter and presentation characteristics other barriers were extrinsic to the program such as poor connectivity, poor infrastructure in health facilities and negative attitudes towards ECHO. Improving on intrinsic factors and mitigating extrinsic factors may help improve ECHO outcomes and scale-up plans.

Circumstances for treatment and control of invasive Enterobacterales infections in eight hospitals across sub-Saharan Africa: a cross-sectional study.

Background: Bloodstream infections caused by Enterobacterales show high frequency of antimicrobial resistance (AMR) in many Low- and Middle-Income Countries. We aimed to describe the variation in circumstances for management of such resistant infections in a group of African public-sector hospitals participating in a major research study. Methods: We gathered data from eight hospitals across sub-Saharan Africa to describe hospital services, infection prevention and antibiotic stewardship activities, using two WHO-generated tools. We collected monthly cross-sectional data on availability of antibiotics in the hospital pharmacies for bloodstream infections caused by Enterobacterales. We compared the availability of these antibiotics to actual patient-level use of antibiotics in confirmed Enterobacterales bloodstream infections (BSI). Results: Hospital circumstances for institutional management of resistant BSI varied markedly. This included self-evaluated infection prevention level (WHO-IPCAF score: median 428, range 155 to 687.5) and antibiotic stewardship activities (WHO stewardship toolkit questions: median 14.5, range 2 to 23). These results did not correlate with national income levels. Across all sites, ceftriaxone and ciprofloxacin were the most consistently available antibiotic agents, followed by amoxicillin, co-amoxiclav, gentamicin and co-trimoxazole. There was substantial variation in the availability of some antibiotics, especially carbapenems, amikacin and piperacillin-tazobactam with degree of access linked to national income level. Investigators described out-of-pocket payments for access to additional antibiotics at 7/8 sites. The in-pharmacy availability of antibiotics correlated well with actual use of antibiotics for treating BSI patients. Conclusions: There was wide variation between these African hospitals for a range of important circumstances relating to treatment and control of severe bacterial infections, though these did not all correspond to national income level. For most antibiotics, patient-level use reflected in-hospital drug availability, suggesting external antibiotics supply was infrequent. Antimicrobial resistant bacterial infections could plausibly show different clinical impacts across sub-Saharan Africa due to this contextual variation.

Clinical Characteristics and Outcomes of Patients Hospitalized With COVID-19 During the First 4 Waves in Zambia.

Importance: Few epidemiologic studies related to COVID-19 have emerged from countries in Africa, where demographic characteristics, epidemiology, and health system capacity differ from other parts of the world. Objectives: To describe the characteristics and outcomes of patients admitted to COVID-19 treatment centers, assess risk factors for in-hospital death, and explore how treatment center admissions were affected by COVID-19 waves in Zambia. Design, Setting, and Participants: This retrospective cohort study assessed patients admitted to COVID-19 treatment centers in 5 Zambian cities between March 1, 2020, and February 28, 2022. Exposures: Risk factors for in-hospital mortality, including patient age and severity of COVID-19, at treatment center admission. Main Outcomes and Measures: Patient information was collected, including inpatient disposition (discharged or died). Differences across and within COVID-19 waves were assessed. Mixed-effects logistic regression models were used to assess associations between risk factors and in-hospital mortality as well as between characteristics of admitted patients and timing of admission. Results: A total of 3876 patients were admitted during 4 COVID-19 waves (mean [SD] age, 50.6 [19.5] years; 2103 male [54.3%]). Compared with the first 3 waves (pooled), the proportion of patients who were 60 years or older admitted during wave 4, when the Omicron variant was circulating, was significantly lower (250 of 1009 [24.8%] vs 1116 of 2837 [39.3%]; P < .001). Factors associated with in-hospital mortality included older age (≥60 vs <30 years; adjusted odds ratio [aOR], 3.55; 95% CI, 2.34-5.52) and HIV infection (aOR, 1.39; 95% CI, 1.07-1.79). Within waves, patients who were admitted during weeks 5 to 9 had significantly higher odds of being 60 years or older (aOR, 2.09; 95% CI, 1.79-2.45) or having severe COVID-19 at admission (aOR, 2.49; 95% CI, 2.14-2.90) than those admitted during the first 4 weeks. Conclusions and Relevance: The characteristics of admitted patients during the Omicron wave and risk factors for in-hospital mortality in Zambia reflect data reported elsewhere. Within-wave analyses revealed a pattern in which it appeared that admission of higher-risk patients was prioritized during periods when there were surges in demand for health services during COVID-19 waves. These findings support the need to expand health system capacity and improve health system resiliency in Zambia and other countries with resource-limited health systems.

COVID-19 Vaccine Effectiveness Against Progression to In-Hospital Mortality in Zambia, 2021-2022.

Background: Coronavirus disease 2019 (COVID-19) vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data are limited from Sub-Saharan Africa. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. Methods: We conducted a retrospective cohort study among admitted patients at 8 COVID-19 treatment centers across Zambia during April 2021 through March 2022, when the Delta and Omicron variants were circulating. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, hospitalization month, and COVID-19 treatment center. Vaccine effectiveness of ≥1 vaccine dose was calculated from the adjusted odds ratio. Results: Among 1653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received ≥1 vaccine dose before hospital admission. Of the patients who had received ≥1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (P < .01). The median time since receipt of a first vaccine dose (interquartile range) was 52.5 (28-107) days. Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI, 42.3%-79.4%). Conclusions: Among patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating the benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.

Clinical presentation and outcomes of syphilitic meningitis among hospitalized adults in lusaka, Zambia.

BACKGROUND: Few studies exist to describe the characteristics of symptomatic syphilitic meningitis, particularly in sub-Saharan Africa, despite a global resurgence. METHODS: We conducted a retrospective analysis of a cohort of adults with meningitis presenting to Zambia's largest referral hospital between April 2014 and December 2017. Individuals with pyogenic bacterial and cryptococcal meningitis were excluded from this cohort. We calculated the prevalence of syphilitic meningitis in the cohort and described the demographic, clinical and laboratory characteristics and outcomes. RESULTS: Of 512 participants, 273 were male, mean age was 37 ± 11 years and 84% were people living with HIV. The prevalence of syphilitic meningitis was 5% with in-hospital and 1-year mortality of 17% and 53%, respectively. Participants with syphilitic meningitis had lower Glasgow Coma Scores than those with other forms of meningitis. Among people living with HIV, those with syphilitic meningitis were less likely to have meningismus and had higher CSF white cell counts. CONCLUSIONS: Syphilitic meningitis was found in 5% of Zambian adults presenting with non-pyogenic bacterial meningitis and non-cryptococcal meningitis, and one-year mortality was high. A high degree of clinical suspicion for syphilitic meningitis in all individuals with meningitis in Zambia is recommended, especially in people living with HIV.

COVID-19 Vaccine Effectiveness during a Prison Outbreak when Omicron was the Dominant Circulating Variant-Zambia, December 2021.

During a COVID-19 outbreak in a prison in Zambia from December 14 to 19, 2021, a case-control study was done to measure vaccine effectiveness (VE) against infection and symptomatic infection, when the Omicron variant was the dominant circulating variant. Among 382 participants, 74.1% were fully vaccinated, and the median time since full vaccination was 54 days. There were no hospitalizations or deaths. COVID-19 VE against any SARS-CoV-2 infection was 64.8%, and VE against symptomatic SARS-CoV-2 infection was 72.9%. COVID-19 vaccination helped protect incarcerated persons against SARS-CoV-2 infection during an outbreak while Omicron was the dominant variant in Zambia. These findings provide important local evidence that might be used to increase COVID-19 vaccination in Zambia and other countries in Africa.

Treatment-Experienced Patients on Third-Line Therapy: A Retrospective Cohort of Treatment Outcomes at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era.

Evaluation of SARS-CoV-2 diagnostics and risk factors associated with SARS-CoV-2 infection in Zambia.

OBJECTIVES: To conduct a diagnostic validation study of SARS-CoV-2 diagnostic kits. METHODS: We compared SARS-CoV-2 diagnostic test results from 3 RT-PCR assays used by the Zambian government between November 2020 and February 2021 (Panther Fusion assay, Da An Gene's 2019-nCoV RNA kit and Maccura's PCR Kit) with the Altona RealStar RT-PCR kit which served as the gold standard. We also evaluated results from rapid antigen testing and whether comorbidities were linked with increased odds of infection. RESULTS: We recruited 244 participants, 61% (149/244) were positive by at least 1 PCR assay. Da An Gene, Maccura, and Panther Fusion assays had sensitivities of 0.0% (95% confidence interval [CI] 0%-41%), 27.1% (95% CI 15%-42%), and 76% (95% CI 65%-85%), respectively, but specificity was low (<85% for all 3 assays). HIV and TB were not associated with SARS-CoV-2, whereas female sex (OR 0.5 [0.3-0.9], p = 0.026) and chronic pulmonary disease (0.1 [0.0-0.8], p = 0.031) were associated with lower odds of SARS-CoV-2 infection. Of 44 samples, 84% sequenced were Beta variant. CONCLUSIONS: The RT-PCR assays evaluated did not meet WHO recommended minimum sensitivity of 80%. Local diagnostic validation studies should be embedded within preparedness plans for future outbreaks to improve the public health response.