COVID-19 Outcomes among People Living with HIV in Colorado.

It is known that people who are immunocompromised or have a comorbidity are at an increased risk for acquiring COVID-19, having a longer duration of COVID-19 symptoms, and a greater likelihood of severe outcomes, including people living with HIV (PLHIV) (Centers for Disease Control and Prevention. (n.d.). Basics of covid-19. Centers for Disease Control and Prevention. Retrieved October 31. 2022, from https://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19/basics-covid-19.html ). However, treatment for PLHIV can greatly reduce the amount of HIV in a person's blood, known as viral suppression. This study compared the outcome of COVID-associated hospitalization among virally suppressed and unsuppressed PLHIV in Colorado. A retrospective cohort analysis was conducted including all known PLHIV in Colorado that were diagnosed with COVID-19 between March 2020 and September 2022. Relevant covariates were identified including race/ethnicity, age at time of diagnosis, region of diagnosis, and vaccination status. An initial univariate logistic regression was then built to test the statistical significance of the association between viral suppression and hospitalization. The final model included all associated covariates and crude and adjusted odds ratios were analyzed. When controlling for covariates, PLHIV who were not virally suppressed at the time of their COVID-19 diagnosis were 2.5 (OR 2.5, 95% CI 1.6-4.0) times as likely to be hospitalized at the time of their first COVID-19 diagnosis compared to those that were suppressed. These findings suggest that viral suppression among PLHIV is protective against poor COVID-19 outcomes. This study is an important first step in highlighting the importance of PLHIV being retained in care and achieving viral suppression in reducing hospitalizations due to COVID-19 in Colorado.

Effect of Test and Treat on clinical outcomes in Nigeria: A national retrospective study.

BACKGROUND: In Nigeria, results from the pilot of the Test and Treat strategy showed higher loss to follow up (LTFU) among people living with HIV compared to before its implementation. The aim of this evaluation was to assess the effects of antiretroviral therapy (ART) initiation within 14 days on LTFU at 12 months and viral suppression. METHODS: We conducted a retrospective cohort study using routinely collected de-identified patient-level data hosted on the Nigeria National Data Repository from 1,007 facilities. The study population included people living with HIV age ≥15. We used multivariable Cox proportional frailty hazard models to assess time to LTFU comparing ART initiation strategy and multivariable log-binomial regression for viral suppression. RESULTS: Overall, 26,937 (38.13%) were LTFU at 12 months. Among individuals initiated within 14 days, 38.4% were LTFU by 12 months compared to 35.4% for individuals initiated >14 days (p<0.001). In the adjusted analysis, individuals who were initiated ≤14 days after HIV diagnosis had a higher hazard of being LTFU (aHR 1.15, 95% CI 1.10-1.20) than individuals initiated after 14 days of HIV diagnosis. Among individuals with viral load results, 86.2% were virally suppressed. The adjusted risk ratio for viral suppression among individuals who were initiated ≤14 days compared to >14 days was not statistically significant. CONCLUSION: LTFU was higher among individuals who were initiated within 14 days compared to greater than 14 days after HIV diagnosis. There was no difference for viral suppression. The provision of early tailored interventions to support newly diagnosed people living may contribute to reducing LTFU.

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.

From Paper Files to Web-Based Application for Data-Driven Monitoring of HIV Programs: Nigeria's Journey to a National Data Repository for Decision-Making and Patient Care.

BACKGROUND: Timely and reliable data are crucial for clinical, epidemiologic, and program management decision making. Electronic health information systems provide platforms for managing large longitudinal patient records. Nigeria implemented the National Data Repository (NDR) to create a central data warehouse of all people living with human immunodeficiency virus (PLHIV) while providing useful functionalities to aid decision making at different levels of program implementation. OBJECTIVE: We describe the Nigeria NDR and its development process, including its use for surveillance, research, and national HIV program monitoring toward achieving HIV epidemic control. METHODS: Stakeholder engagement meetings were held in 2013 to gather information on data elements and vocabulary standards for reporting patient-level information, technical infrastructure, human capacity requirements, and information flow. Findings from these meetings guided the development of the NDR. An implementation guide provided common terminologies and data reporting structures for data exchange between the NDR and the electronic medical record (EMR) systems. Data from the EMR were encoded in extensible markup language and sent to the NDR over secure hypertext transfer protocol after going through a series of validation processes. RESULTS: By June 30, 2021, the NDR had up-to-date records of 1,477,064 (94.4%) patients receiving HIV treatment across 1,985 health facilities, of which 1,266,512 (85.7%) patient records had fingerprint template data to support unique patient identification and record linkage to prevent registration of the same patient under different identities. Data from the NDR was used to support HIV program monitoring, case-based surveillance and production of products like the monthly lists of patients who have treatment interruptions and dashboards for monitoring HIV test and start. CONCLUSION: The NDR enabled the availability of reliable and timely data for surveillance, research, and HIV program monitoring to guide program improvements to accelerate progress toward epidemic control.

Individual and household factors associated with non-disclosure of positive HIV status in a population-based HIV serosurvey.

OBJECTIVES: Non-disclosure of positive HIV status in population-based surveys causes underestimation of national HIV diagnosis and biases inferences about engagement in the care continuum. This study investigated individual and household factors associated with HIV non-disclosure to survey interviewers in Nigeria. DESIGN: Secondary analysis of a cross sectional population-based household HIV survey. METHODS: We analyzed data from adults aged 15-64 years who tested positive for HIV and had antiretroviral drugs (ARVs) in their blood from a nationally representative HIV sero-survey conducted in Nigeria in 2018. We considered ARV use as a proxy for knowledge of HIV diagnosis; thus, respondents who self-reported to be unaware of their HIV status were classified as non-disclosers. We estimated the associations between non-disclosure and various sociodemographic, clinical, and household characteristics using weighted logistic regression. RESULTS: Among 1266 respondents living with HIV who were taking ARVs, 503 (40%) did not disclose their HIV status to interviewers. In multivariable statistical analyses, the adjusted odds of non-disclosure were highest among respondents aged 15-24 years, those with less than a primary school education, and those who were the only person living with HIV in their household. CONCLUSIONS: Non-disclosure of positive HIV status to survey personnel is common among adults who are receiving treatment in Nigeria. These findings highlight the importance of validating self-reported HIV status in surveys using biomarkers of ARV use. Meanwhile, it is crucial to improve disclosure by strengthening interview procedures and tailoring strategies towards groups that are disproportionately likely to underreport HIV diagnoses.

Assessment of safety and effectiveness of non-neurosurgical management for minimal traumatic brain injury (TBI).

BACKGROUND: Patients with mild traumatic brain injury (TBI) and intracranial hemorrhage often receive neurosurgical consultation. However, only a small proportion of patients require intervention. Our hypothesis is that low-risk minimal TBI patients managed without immediate neurosurgical consultation will have a reasonable safety and effectiveness outcome profile. METHODS: A non-neurosurgical management protocol for adult minimal TBI was implemented at a level I trauma center as an interdisciplinary quality-improvement initiative in November 2018. Minimal TBI was defined as Glasgow Coma Scale (GCS) of 15 secondary to blunt mechanism, without anticoagulant or antiplatelet therapy, and isolated pneumocephalus and/or traumatic subarachnoid hemorrhage on head CT imaging. Safety was assessed by in-hospital mortality, neurosurgical interventions, and ED revisits within two weeks of discharge. Effectiveness was assessed by neurosurgical consult rate and length of stay. Outcomes were compared 8-months pre- and post-protocol implementation. RESULTS: A total of 97 patients were included, of which 49 were pre-protocol and 48 were post-protocol There was no difference in rates of in-hospital mortality [0 (0%) vs 0 (0%)], neurosurgical procedure [1 (2.1%) vs 0 (0%)], operations [0 (0%) vs 0 (0%)], and ED revisits [1 (2.0%) vs 2 (4.2%), p = 0.985] between the periods. There was a significant reduction in neurosurgical consults post-protocol implementation (92% vs 29%, p<0.001). CONCLUSION: A protocol for minimal TBI patients effectively reduced neurosurgical consultation without changes in safety profile. Such an interdisciplinary management protocol for low-risk neurotrauma can effectively utilize the neurosurgery consult services by stratifying neurologically stable TBI patient.

Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study.

BACKGROUND: HIV transmission can occur with a viral load of at least 200 copies per mL of blood and low-level viraemia can lead to virological failure; the threshold level at which risk for virological failure is conferred is uncertain. To better understand low-level viraemia prevalence and outcomes, we analysed retrospective longitudinal data from a large cohort of people living with HIV on antiretroviral therapy (ART) in Nigeria. METHODS: In this retrospective cohort study using previously collected longitudinal patient data, we estimated rates of virological suppression (≤50 copies per mL), low-level viraemia (51-999 copies per mL), virological non-suppression (≥1000 copies per mL), and virological failure (≥2 consecutive virological non-suppression results) among people living with HIV aged 18 years and older who initiated and received at least 24 weeks of ART at 1005 facilities in 18 Nigerian states. We analysed risk for low-level viraemia, virological non-suppression, and virological failure using log-binomial regression and mixed-effects logistic regression. FINDINGS: At first viral load for 402 668 patients during 2016-21, low-level viraemia was present in 64 480 (16·0%) individuals and virological non-suppression occurred in 46 051 (11·4%) individuals. Patients with low-level viraemia had increased risk of virological failure (adjusted relative risk 2·20, 95% CI 1·98-2·43; p<0·0001). Compared with patients with virological suppression, patients with low-level viraemia, even at 51-199 copies per mL, had increased odds of low-level viraemia and virological non-suppression at next viral load; patients on optimised ART (ie, integrase strand transfer inhibitors) had lower odds than those on non-integrase strand transfer inhibitors for the same low-level viraemia range (eg, viral load ≥1000 copies per mL following viral load 400-999 copies per mL, integrase strand transfer inhibitor: odds ratio 1·96, 95% CI 1·79-2·13; p<0·0001; non-integrase strand transfer inhibitor: 3·21, 2·90-3·55; p<0·0001). INTERPRETATION: Patients with low-level viraemia had increased risk of virological non-suppression and failure. Programmes should revise monitoring benchmarks and targets from less than 1000 copies per mL to less than 50 copies per mL to strengthen clinical outcomes and track progress to epidemic control. FUNDING: None.

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.

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.

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.

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.

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.

Sex Differences in HIV Testing - 20 PEPFAR-Supported Sub-Saharan African Countries, 2019.

Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

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.

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.

Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella.

Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity.

Mental Illness and Mental Health Defenses: Perceptions of the Criminal Bar.

As the number of state mental hospital beds declines, persons with persistent mental illness are increasingly encountered by those working in the legal system. Attorneys may have little experience in working with this population. This research involved a 32-item written survey of the 492 members of the criminal bar in South Carolina. Demographic variables were surveyed, and attorneys were asked to define two common terms describing mental illnesses (delusion and psychosis) and the legal criteria for verdicts of not guilty by reason of insanity and guilty but mentally ill. They were also asked to identify the most severe mental illness (schizophrenia). Attitudes about these verdicts and about working with defendants who are mentally ill were also surveyed. Results indicate that attorneys are fairly knowledgeable about mental illness, but not verdicts involving mental illness, particularly the verdict of guilty but mentally ill. Most attorneys prefer to work with clients who do not have mental illness. However, as they become more experienced interacting with defendants who are affected by mental illness, they become more knowledgeable and are more willing to defend them. A large majority believe that their law school education about mental illness was inadequate. When comparing attorney occupations, public defenders were the most knowledgeable about mental illness and mental health defenses, followed by prosecutors and private defense attorneys. Judges were the least knowledgeable group.

Rural health care in New Zealand: the case of Coast to Coast Health Centre, Wellsford, an early Integrated Family Health Centre.

INTRODUCTION: Primary health care is critical, particularly in rural areas distant from secondary care services. AIM: To describe the development of Coast to Coast Health Centre (CTCHC) at Wellsford, north of Auckland, New Zealand and reflect on its achievements and ongoing challenges. METHODS: Interviews were conducted with staff and management of CTCHC and with other health service providers. Surveys of staff and a sample of enrolled patients were undertaken. Numerical data on service utilisation were obtained from the practice and from national datasets. RESULTS: The CTCHC provides a wide range of services, including after-hours care, maternity and radiology, across a network of electronically connected sites, as well as interdisciplinary training for a range of health students. General practitioner (GP) recruitment is problematic and nursing roles have been expanded. Staff report positively on the work environment. Consultation rates are higher than in comparable practices, especially consultations with nurses. Rates of hospital admission are relatively low. The development of the CTCHC was assisted by formation of a local primary health organisation (PHO) and by recognition by the local district health board (DHB). Issues with poor coordination of local services, and less service provision than is characteristic in urban areas, remain. Contracting processes with the DHB were complex and time-consuming. The merging of the local PHO into a larger PHO within the Waitemata DHB catchment inhibited progression towards more complete locality planning. DISCUSSION: A dedicated and locally controlled provider was able to generate a more than usually complete community health service for Wellsford and area.