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.

Evaluation of the Acute flaccid paralysis surveillance indicators in Zambia from 2015-2021: a retrospective analysis.

BACKGROUND: The resurgence of poliovirus infection in previously polio free regions and countries calls for renewed commitment to the global polio eradication efforts including strengthening of Acute Flaccid Paralysis (AFP) surveillance systems. Zambia is one of the countries substantially at risk for the importation of poliovirus infection from neighbouring countries including Malawi, Mozambique, and Democratic Republic of the Congo (DRC). This study describes a seven-year AFP surveillance, assesses the surveillance indicators, and highlights areas for improvement. METHODS: We conducted retrospective analysis of the routinely collected AFP surveillance data from January 2015 to December 2022. The AFP surveillance indicators performance was assessed using the World Health Organisation's recommended minimum AFP surveillance indicators performance. RESULTS: Cumulatively, a total of 1715 AFP cases were reported over the study period. More than half, 891 (52%) of reported cases were aged < 5 years with 917 (53.5%) of males. More than half, 1186 (69.2%) had fever at onset, 718 (41.9%) had asymmetric paralysis and 1164 (67.9%) had their paralysis progressed within 3 days of onset. The non-polio AFP rate ranges from 3.4 to 6.4 per 100,000 children < 15 years old and stool adequacy ranging from 70.9% to 90.2% indicating sensitive surveillance with late detection of cases. The percentage of cases with early stool collection, timely transportation was above the World Health Organisation (WHO) minimum of 80% but with declining proportion of stools arriving in the laboratory in optimal condition. Completeness of 60-days follow-up evaluation was suboptimal ranging from 0.9% to 28.2%. CONCLUSION: The AFP surveillance system in Zambia is doing well. However, additional efforts are needed to improve early detection of cases; stool sample collection, transportation and monitoring to ensure arrival in good condition in the laboratory; and improve 60-days follow-up evaluation for evidenced-based classification of inadequate AFP cases and proper care.

Leveraging health infrastructure to optimize HPV vaccination for adolescents in Zambia: Protocol for an implementation study.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14-15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents-those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination schedule for ALHIV (3 versus 2 doses). Integrating HPV vaccination into routine care in adolescent HIV clinics may ensure that ALHIV have access to vaccine at the WHO-recommended schedule. Such integration requires a multilevel approach, stakeholder engagement, and diversified implementation strategies, given known challenges of providing the HPV vaccine in LMICs, including Zambia. METHODS: Our study aims to integrate HPV vaccination into routine care in adolescent HIV clinics. To achieve success, we will co-design a package of implementation strategies using a previously successful implementation research approach developed for cervical cancer prevention in LMICs: the Integrative Systems Praxis for Implementation Research (INSPIRE). INSPIRE is a novel, comprehensive approach to develop, implement, and evaluate implementation science efforts. Following key elements of INSPIRE, our specific aims are to: 1) Identify the unique multilevel contextual factors (barriers and facilitators) across HIV settings (rural, urban, peri-urban) that influence HPV vaccine uptake; 2) Use Implementation Mapping to translate stakeholder feedback and findings from Aim 1 into a package of implementation strategies to integrate HPV vaccine into HIV clinics; 3) Conduct a Hybrid Type 3 effectiveness-implementation trial to evaluate the package of multilevel implementation strategies for integrating HPV vaccine into HIV clinics. DISCUSSION: Our research team has strong support, technical expertise, and resources (e.g., vaccines) from the Zambian Ministry of Health; and political will for scale-up. This stakeholder-based implementation model has the potential to be transported to HIV clinics across Zambia and serve as a model to address cancer prevention priorities for those with HIV in other LMICs. TRIAL REGISTRATION: To be registered prior to Aim 3, when implementation strategies finalized.

Optimizing and validating a pediatric screening tool to more efficiently test and identify children living with HIV.

OBJECTIVE: To develop and validate a screening tool to improve testing efficiency and increase case finding of children living with HIV. DESIGN: Cross-sectional study. METHODS: Between November 2020 and September 2021, children 18 months to 14 years presenting at outpatient departments in 30 health facilities in Zambia were administered a 14-question pediatric HIV screening tool and then tested for HIV. Data were analyzed using a randomly extracted 'validation' dataset and multivariable logistic regression to determine the highest performing and optimal number of screening questions. The final tool was then evaluated in the 'test' dataset. Sensitivity and specificity were calculated for both datasets. The final tool was then also implemented in 12 additional facilities to determine operational feasibility and uptake. RESULTS: A total of 9902 children were included in the final analysis. HIV prevalence was 1.3%. Six questions were significantly associated with HIV-positivity. The optimal screening cutoff score was to answer 'yes' to one or more of the six questions; using this cutoff sensitivity was 92.5% [95% confidence interval (CI) 85.7-96.7%] and specificity was 62.9% (95% CI 61.9-64%). In the test dataset, the same tool had a sensitivity of 84.6% (95% CI 65.1-95.6%) and specificity of 64.6% (95% CI 62.4-66.7%). Uptake was 89%. CONCLUSION: The results of this study show sensitivity and acceptable specificity in a six-question validated HIV screening tool. Implementing this screening tool in settings where universal testing is not feasible should more efficiently accelerate identification of children living with HIV (CLHIV) and their timely initiation onto life-saving drugs.

Update on Wild Poliovirus Type 1 Outbreak - Southeastern Africa, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

Challenges Addressing Inequalities in Measles Vaccine Coverage in Zambia through a Measles-Rubella Supplementary Immunization Activity during the COVID-19 Pandemic.

BACKGROUND: Measles-rubella supplementary immunization activities (MR-SIAs) are conducted to address inequalities in coverage and fill population immunity gaps when routine immunization services fail to reach all children with two doses of a measles-containing vaccine (MCV). We used data from a post-campaign coverage survey in Zambia to measure the proportion of measles zero-dose and under-immunized children who were reached by the 2020 MR-SIA and identified reasons associated with persistent inequalities following the MR-SIA. METHODS: Children between 9 and 59 months were enrolled in a nationally representative, cross-sectional, multistage stratified cluster survey in October 2021 to estimate vaccination coverage during the November 2020 MR-SIA. Vaccination status was determined by immunization card or through caregivers' recall. MR-SIA coverage and the proportion of measles zero-dose and under-immunized children reached by MR-SIA were estimated. Log-binomial models were used to assess risk factors for missing the MR-SIA dose. RESULTS: Overall, 4640 children were enrolled in the nationwide coverage survey. Only 68.6% (95% CI: 66.7%, 70.6%) received MCV during the MR-SIA. The MR-SIA provided MCV1 to 4.2% (95% CI: 0.9%, 4.6%) and MCV2 to 6.3% (95% CI: 5.6%, 7.1%) of enrolled children, but 58.1% (95% CI: 59.8%, 62.8%) of children receiving the MR-SIA dose had received at least two prior MCV doses. Furthermore, 27.8% of measles zero-dose children were vaccinated through the MR-SIA. The MR-SIA reduced the proportion of measles zero-dose children from 15.1% (95% CI: 13.6%, 16.7%) to 10.9% (95% CI: 9.7%, 12.3%). Zero-dose and under-immunized children were more likely to miss MR-SIA doses (prevalence ratio (PR): 2.81; 95% CI: 1.80, 4.41 and 2.22; 95% CI: 1.21 and 4.07) compared to fully vaccinated children. CONCLUSIONS: The MR-SIA reached more under-immunized children with MCV2 than measles zero-dose children with MCV1. However, improvement is needed to reach the remaining measles zero-dose children after SIA. One possible solution to address the inequalities in vaccination is to transition from nationwide non-selective SIAs to more targeted and selective strategies.

Leveraging HIV Program and Civil Society to Accelerate COVID-19 Vaccine Uptake, Zambia.

To accelerate COVID-19 vaccination delivery, Zambia integrated COVID-19 vaccination into HIV treatment centers and used World AIDS Day 2021 to launch a national vaccination campaign. This campaign was associated with significantly increased vaccinations, demonstrating that HIV programs can be leveraged to increase COVID-19 vaccine uptake.

Effectiveness of two doses of Euvichol-plus oral cholera vaccine in response to the 2017/2018 outbreak: a matched case-control study in Lusaka, Zambia.

INTRODUCTION: Zambia experienced a major cholera outbreak in 2017-2018, with more than 5905 cases reported countrywide, predominantly from the peri-urban slums of Lusaka city. The WHO recommends the use of oral cholera vaccines (OCVs) together with traditional control measures, including health promotion, provision of safe water and improving sanitation, in cholera endemic areas and during cholera outbreaks. In response to this outbreak, the Zambian government implemented the OVC campaign and administered the Euvichol-plus vaccine in the high-risk subdistricts of Lusaka. Although OCVs have been shown to be effective in preventing cholera infection in cholera endemic and outbreak settings, the effectiveness of the Euvichol-plus vaccine has not yet been evaluated in Zambia. This study aimed to determine the effectiveness of two doses of OCV administered during the 2017/2018 vaccination campaign. METHODS: We conducted a matched case-control study involving 79 cases and 316 controls following the mass vaccination campaign in the four subdistricts of Lusaka (Chawama, Chipata, Kanyama and Matero). Matching of controls was based on the place of residence, age and sex. Conditional logistic regression was used for analysis. Adjusted OR (AOR), 95% CI and vaccine effectiveness (1-AOR) for two doses of Euvichol-plus vaccine and any dose were estimated (p<0.05). RESULTS: The AOR vaccine effectiveness for two doses of Euvichol-plus OCV was 81.0% (95% CI 66.0% to 78.0%; p<0.01). Secondary analysis showed that vaccine effectiveness for any dose was 74.0% (95% CI 50.0% to 86.0%; p<0.01). CONCLUSION: These findings show that two doses of Euvichol-plus OCV are effective in a cholera outbreak setting in Lusaka, Zambia. The findings also indicate that two doses are more effective than a single dose and thus support the use of two doses of the vaccine as part of an integrated intervention to cholera control during outbreaks.

Improving management of vaccine supply chains: A multi-methods evaluation of vSTEP in Zambia.

BACKGROUND: Equipping supply chain professionals at all levels of the health care systems with essential leadership and management skills is essential to achieving global immunization targets. Numerous and diverse professional development initiatives have been established to support vaccine supply chain managers in Gavi-eligible countries. However, COVID-19 catalyzed rapid innovation in approaches to support leadership development in times of rapid change, and systematic evaluation of these approaches can inform future workforce development strategies to ensure resilient health systems. Therefore, we sought to evaluate outcomes and short-term impact of the fully virtual Strategic Training Executive Program 2.0 (vSTEP 2.0) program in Zambia on participant engagement, skill development, and application of new skills to improve supply chain performance. METHODS: We used a multi-method design to describe the outcomes and short-term impact of vSTEP 2.0 at three levels: (1) delegate response to the training experience (including participation, completion, and satisfaction); (2) delegate change in leadership skill (including achievement of learning objectives and change in competencies); and (3) application of new skills to impact supply chain performance. RESULTS: The program achieved high levels of engagement and an 83% graduation rate despite the length and rigor of the program. High satisfaction was evidenced by positive feedback from delegates on the quality and relevance of the program, especially in the context of COVID response (100% would "definitely" recommend). Delegates demonstrated significant growth in all domains of leadership competencies and applied their learnings to address a complex challenge in supply chain performance in their home organization. DISCUSSION: These findings demonstrate a strong appetite for leadership development support among vaccine supply chain professionals, especially in times of rapid change such as during the COVID response. These results also demonstrate the feasibility and impact of a fully virtual model for leadership development, with implications well beyond the COVID-19 pandemic.