SARS-CoV-2 Prevalence among Outpatients during Community Transmission, Zambia, July 2020.

During the July 2020 first wave of severe acute respiratory syndrome coronavirus 2 in Zambia, PCR-measured prevalence was 13.4% among outpatients at health facilities, an absolute difference of 5.7% compared with prevalence among community members. This finding suggests that facility testing might be an effective strategy during high community transmission.

COVID-19 Severity and COVID-19-Associated Deaths Among Hospitalized Patients with HIV Infection - Zambia, March-December 2020.

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

Expanding access to HIV services during the COVID-19 pandemic-Nigeria, 2020.

BACKGROUND: To accelerate progress toward the UNAIDS 90-90-90 targets, US Centers for Disease Control and Prevention Nigeria country office (CDC Nigeria) initiated an Antiretroviral Treatment (ART) Surge in 2019 to identify and link 340,000 people living with HIV/AIDS (PLHIV) to ART. Coronavirus disease 2019 (COVID-19) threatened to interrupt ART Surge progress following the detection of the first case in Nigeria in February 2020. To overcome this disruption, CDC Nigeria designed and implemented adapted ART Surge strategies during February-September 2020. METHODS: Adapted ART Surge strategies focused on continuing expansion of HIV services while mitigating COVID-19 transmission. Key strategies included an intensified focus on community-based, rather than facility-based, HIV case-finding; immediate initiation of newly-diagnosed PLHIV on 3-month ART starter packs (first ART dispense of 3 months of ART); expansion of ART distribution through community refill sites; and broadened access to multi-month dispensing (MMD) (3-6 months ART) among PLHIV established in care. State-level weekly data reporting through an Excel-based dashboard and individual PLHIV-level data from the Nigeria National Data Repository facilitated program monitoring. RESULTS: During February-September 2020, the reported number of PLHIV initiating ART per month increased from 11,407 to 25,560, with the proportion found in the community increasing from 59 to 75%. The percentage of newly-identified PLHIV initiating ART with a 3-month ART starter pack increased from 60 to 98%. The percentage of on-time ART refill pick-ups increased from 89 to 100%. The percentage of PLHIV established in care receiving at least 3-month MMD increased from 77 to 93%. Among PLHIV initiating ART, 6-month retention increased from 74 to 92%. CONCLUSIONS: A rapid and flexible HIV program response, focused on reducing facility-based interactions while ensuring delivery of lifesaving ART, was critical in overcoming COVID-19-related service disruptions to expand access to HIV services in Nigeria during the first eight months of the pandemic. High retention on ART among PLHIV initiating treatment indicates immediate MMD in this population may be a sustainable practice. HIV program infrastructure can be leveraged and adapted to respond to the COVID-19 pandemic.

Increase in Antiretroviral Therapy Enrollment Among Persons with HIV Infection During the Lusaka HIV Treatment Surge - Lusaka Province, Zambia, January 2018-June 2019.

Within Zambia, a landlocked country in southern-central Africa, the highest prevalence of human immunodeficiency virus (HIV) infection is in Lusaka Province (population 3.2 million), where approximately 340,000 persons are estimated to be infected (1). The 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA) estimated the adult HIV prevalence in Lusaka Province to be 15.7%, with a 62.7% viral load suppression rate (HIV-1 RNA <1,000 copies/mL) (2). ZAMPHIA results highlighted remaining treatment gaps in Zambia overall and by subpopulation. In January 2018, Zambia launched the Lusaka Province HIV Treatment Surge (Surge project) to increase enrollment of persons with HIV infection onto antiretroviral therapy (ART). The Zambia Ministry of Health (MoH), CDC, and partners analyzed the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) Monitoring and Evaluation Reporting data set to assess the effectiveness of the first 18 months of the Surge project (January 2018-June 2019). During this period, approximately 100,000 persons with positive test results for HIV began ART. These new ART clients were more likely to be persons aged 15-24 years. In addition, the number of persons with documented viral load suppression doubled from 66,109 to 134,046. Lessons learned from the Surge project, including collaborative leadership, efforts to improve facility-level performance, and innovative strategies to disseminate successful practices, could increase HIV treatment rates in other high-prevalence settings.

Detection of Typhoidal and Paratyphoidal Salmonella in Blood by Real-time Polymerase Chain Reaction.

BACKGROUND: The gold standard for diagnosis of enteric fever caused by Salmonella Typhi or Salmonella Paratyphi A or B is bone marrow culture. However, because bone marrow aspiration is highly invasive, many hospitals and large health centers perform blood culture instead. As blood culture has several limitations, there is a need for novel typhoid diagnostics with improved sensitivity and more rapid time to detection. METHODS: We developed a clyA-based real-time polymerase chain reaction (qPCR) method to detect Salmonella Typhi and Salmonella Paratyphi A simultaneously in blood. The sensitivity and specificity of this probeset was first evaluated in vitro in the laboratory and then in a typhoid-endemic population, in Karachi, Pakistan, and in healthy US volunteers. RESULTS: We optimized a DNA extraction and real-time PCR-based method that could reliably detect 1 colony-forming unit/mL of Salmonella Typhi. The probe set was able to detect clinical Salmonella Typhi and Salmonella Paratyphi A strains and also diarrheagenic Escherichia coli, but not invasive E. coli or other invasive bacteria. In the field, the clyA qPCR diagnostic was 40% as sensitive as blood culture. However, when qPCR-positive specimens were considered to be true positives, blood culture only exhibited 28.57% sensitivity. Specificity was ≥90% for all comparisons and in the healthy US volunteers. qPCR was significantly faster than blood culture in terms of detection of typhoid and paratyphoid. CONCLUSIONS: Based on lessons learned, we recommend that future field trials of this and other novel diagnostics that detect typhoidal and nontyphoidal Salmonella employ multiple methodologies to define a "positive" sample.

Reaching HIV epidemic control in Nigeria using a lower HIV viral load suppression cut-off.

BACKGROUND: Virologic suppression has been defined using a HIV viral load of less than 1000 copies/ml. Low-level viremia (51-999 copies/ml) is associated with an increased risk of virologic failure and HIV drug resistance. METHODS: Retrospective data from persons with HIV (PWH) who initiated ART between January 2016 and September 2022 in Nigeria were analyzed for virologic suppression at cut-off values less than 1000 copies/ml. RESULTS: In 2022, virologic suppression at less than 1000 copies/ml was 95.7%. Using cut-off values of less than 400, less than 200 and less than 50 copies/ml, virologic suppression was 94.2%, 92.5%, and 87%, respectively. DISCUSSION: Monitoring virologic suppression using lower cut-off values, alongside differentiated management of low-level viremia, may help Nigeria achieve HIV epidemic control targets.

Peritonitis and technique failure caused by Roseomonas mucosa in an adolescent infected with HIV on continuous cycling peritoneal dialysis.

We report the first case of peritonitis caused by Roseomonas mucosa which led to technique failure in an adolescent patient with HIV receiving peritoneal dialysis. Identification of the causative organism by 16S rRNA gene sequencing and phylogenetic analysis is described.

A national HIV clinical mentorship program: Enabling Zambia to accelerate control of the HIV epidemic.

Although Zambia has increased the proportion of people living with HIV (PLHIV) who are on antiretroviral therapy (ART) in recent years, progress toward HIV epidemic control remains inconsistent. Some districts are still failing to meet the UNAIDS 90/90/90 targets where 90% of PLHIV should know their status, 90% of those diagnosed should be on ART, and 90% of those on ART should achieve viral load suppression (VLS) by 2020. Providing consistently excellent HIV services at all ART health facilities is critical for achieving the UNAIDS 90/90/90 targets and controlling the HIV epidemic in Zambia. Zambia Ministry of Health, in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), aimed to achieve these targets through establishing a national HIV clinical mentorship program in which government-employed mentors were assigned to specific facilities with a mandate to identify and ameliorate programmatic challenges. Mentors were hired, trained and deployed to individual facilities in four provinces to mentor staff on quality HIV clinical and program management. The pre-mentorship period was July 2018-September 2018 and the post-mentorship period was July 2019-September 2019. Review of key programmatic indicators from the pre and post-deployment periods revealed the proportion of people who had a positive HIV test result out of those tested increased from 4.2% to 6.8% (P <0.001) as fewer HIV tests were needed despite the number of PLHIV being identified and placed on ART increasing from 492,613 to 521,775, and VLS increased from 84.8% to 90.1% (p <0.001). Key considerations in the establishment of an HIV clinical mentorship program include having a government-led process of regular site level data review and continuous clinical mentorship underpinned by quality improvement methodology.

A Quality Improvement Collaborative for Adolescents Living With HIV to Improve Immediate Antiretroviral Therapy Initiation at 25 Health Facilities in Lusaka, Zambia.

ABSTRACT: HIV testing with rapid antiretroviral therapy (ART) initiation are life-saving interventions for adolescents living with HIV. However, in Zambia, HIV diagnosis and immediate ART initiation among adolescents living with HIV is lagging. In collaboration with the Zambian Ministry of Health, the U.S. Health Resources and Services Administration, the U.S. Centers for Disease Control and Prevention in Zambia, and ICAP at Columbia University designed and implemented a quality improvement collaborative (QIC) to improve adolescent immediate ART initiation at 25 health facilities in Lusaka. Over the 12-month implementation period, quality improvement teams tested and identified targeted intervention, that significantly improved ART initiation within 14 days of receiving positive test results, from 24% at baseline to more than 93% for the final 6 months of implementation. The quality improvement collaborative approach empowered health care workers to innovate addressing the root causes of suboptimal performance and produced a package of successful interventions that will be shared throughout Zambia.

Improving Services for HIV-Exposed Infants in Zambia and Cameroon Using a Quality Improvement Collaborative Approach.

INTRODUCTION: Early infant diagnosis (EID) and rapid antiretroviral therapy (ART) initiation are lifesaving interventions for HIV-infected infants. In Cameroon and Zambia, EID coverage for HIV-exposed infants (HEIs) is suboptimal and the time to ART initiation for infants infected with HIV often exceeds national standards despite numerous policy and training initiatives. METHODS: ICAP at Columbia University supported the Cameroon and Zambia Ministries of Health (MOHs) and local partners to implement quality improvement collaboratives (QICs) to improve EID coverage and ART initiation at 17 health facilities (HFs) in Cameroon (March 2016 to June 2017) and 15 HFs in Zambia (March 2017 to June 2018). In each country, MOH led project design and site selection. MOH and ICAP provided quality improvement training and monthly supportive supervision, which enabled HF teams to conduct root cause analyses, design and implement contextually appropriate interventions, conduct rapid tests of change, analyze monthly progress, and convene at quarterly learning sessions to compare performance and share best practices. RESULTS: In Cameroon, EID testing coverage improved from 57% (113/197 HEIs tested) during the 5-month baseline period to 80% (165/207) in the 5-month endline period. In Zambia, EID testing coverage improved from 77% (4,773/6,197) during the 12-month baseline period to 89% (2,144/2,420) during the 3-month endline period. In a comparison of the same baseline and endline periods, the return of positive test results to caregivers improved from 18% (36/196 caregivers notified) to 86% (182/211) in Cameroon and from 44% (94/214) to 79% (44/56) in Zambia. ART initiation improved from 44% (94/214 HIV-infected infants) to 80% (45/56) in Zambia; the numbers of HIV-infected infants in Cameroon were too small to detect meaningful differences. CONCLUSIONS: QICs improved coverage of timely EID and ART initiation in both countries. In addition to building quality improvement capacity and improving outcomes, the QICs resulted in a "change package" of successful initiatives that were disseminated within each country.

Impact of the Saving Mothers, Giving Life Approach on Decreasing Maternal and Perinatal Deaths in Uganda and Zambia.

BACKGROUND: Maternal and perinatal mortality is a global development priority that continues to present major challenges in sub-Saharan Africa. Saving Mothers, Giving Life (SMGL) was a multipartner initiative implemented from 2012 to 2017 with the goal of improving maternal and perinatal health in high-mortality settings. The initiative accomplished this by reducing delays to timely and appropriate obstetric care through the introduction and support of community and facility evidence-based and district-wide health systems strengthening interventions. METHODS: SMGL-designated pilot districts in Uganda and Zambia documented baseline and endline maternal and perinatal health outcomes using multiple approaches. These included health facility assessments, pregnancy outcome monitoring, enhanced maternal mortality detection in facilities, and district population-based identification and investigation of maternal deaths in communities. RESULTS: Over the course of the 5-year SMGL initiative, population-based estimates documented a 44% reduction in the SMGL-supported district-wide maternal mortality ratio (MMR) in Uganda (from 452 to 255 maternal deaths per 100,000 live births) and a 41% reduction in Zambia (from 480 to 284 maternal deaths per 100,000 live births). The MMR in SMGL-supported health facilities declined by 44% in Uganda and by 38% in Zambia. The institutional delivery rate increased by 47% in Uganda (from 45.5% to 66.8% of district births) and by 44% in Zambia (from 62.6% to 90.2% of district births). The number of facilities providing emergency obstetric and newborn care (EmONC) rose from 10 to 26 in Uganda and from 7 to 13 in Zambia, and lower- and mid-level facilities increased the number of EmONC signal functions performed. Cesarean delivery rates increased by more than 70% in both countries, reaching 9% and 5% of all births in Uganda and Zambia districts, respectively. Maternal deaths in facilities due to obstetric hemorrhage declined by 42% in Uganda and 65% in Zambia. Overall, perinatal mortality rates declined, largely due to reductions in stillbirths in both countries; however, no statistically significant changes were found in predischarge neonatal death rates in predischarge either country. CONCLUSIONS: MMRs fell significantly in Uganda and Zambia following the introduction of the SMGL interventions, and SMGL's comprehensive district systems-strengthening approach successfully improved coverage and quality of care for mothers and newborns. The lessons learned from the initiative can inform policy makers and program managers in other low- and middle-income settings where similar approaches could be used to rapidly reduce preventable maternal and newborn deaths.

Opsonophagocytic Assay To Evaluate Immunogenicity of Nontyphoidal Salmonella Vaccines.

Nontyphoidal Salmonella (NTS) invasive infections are an important cause of morbidity and mortality in sub-Saharan Africa. Several vaccines are in development to prevent these infections. We describe an NTS opsonophagocytic killing assay that uses HL-60 cells and baby rabbit complement to quantify functional antibodies elicited by candidate NTS vaccines.

Serum bactericidal assays to evaluate typhoidal and nontyphoidal Salmonella vaccines.

Invasive Salmonella infections for which improved or new vaccines are being developed include enteric fever caused by Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidal Salmonella (NTS) serovars, particularly S. enterica serovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developed in vitro assays to quantify serum bactericidal antibody (SBA) activity induced by S. Typhi, S. Paratyphi A, S. Typhimurium, and S. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. For S. Enteritidis, S. Typhimurium, and S. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast, S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administered S. Typhimurium, S. Enteritidis, and S. Paratyphi A but not S. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited by Salmonella vaccine candidates.

Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques.