COVID-19 vaccine access in Africa: Global distribution, vaccine platforms, and challenges ahead.

Development COVID-19 vaccines in a record time has been an unprecedented global scientific achievement. However, the world has failed to ensure equitable access to what should have been a global public good. What options remain available to African countries to ensure immunization of their populations and ultimately overcome the pandemic?

Africa Needs a New Public Health Order to Tackle Infectious Disease Threats.

The SARS-CoV-2 pandemic has revealed that Africa needs a new public health order to be resilient, to adapt, and to cope with 21st-century disease threats. The new order will need strengthened continental and national public health institutions; local manufacturing of vaccines, therapeutics, and diagnostics; attraction, training, and retention of a public health workforce; and fostering of respectful local and international partnerships.

Field Validation of Limiting-Antigen Avidity Enzyme Immunoassay to Estimate HIV-1 Incidence in Cross-Sectional Survey in Swaziland.

Reliable and accurate laboratory assays to detect recent HIV-1 infection have potential as simple and practical methods of estimating HIV-1 incidence in cross-sectional surveys. This study describes validation of the limiting-antigen (LAg) avidity enzyme immunoassay (EIA) in a cross-sectional national survey, conducted in Swaziland, comparing it to prospective follow-up incidence. As part of the Swaziland HIV-1 Incidence Measurement Survey (SHIMS), 18,172 individuals underwent counseling and HIV rapid testing in a household-based, population survey conducted from December 2010 to June 2011. Plasma samples from HIV-positive persons were classified as recent infections using an incidence testing algorithm with LAg-Avidity EIA (normalized optical density ≤1.5) followed by viral load (VL ≥1,000 copies/mL). All HIV-seronegative samples were tested for acute HIV-1 infection by nucleic acid amplification test (NAAT) pooling. HIV-seronegative individuals who consented to follow-up were retested ∼6 months later to detect observed HIV-1 seroconversion. HIV-1 incidence estimates based on LAg+VL and NAAT were calculated using assay-specific parameters and were compared with prospective incidence estimate. A total of 5,803 (31.9%) of 18,172 survey participants tested HIV seropositive; of these 5,683 (97.9%) were further tested with LAg+VL algorithm. The weighted annualized incidence from the longitudinal cohort study was 2.4% (95% confidence interval 2.0-2.7). Based on cross-sectional testing of HIV positives with LAg+VL algorithm, overall weighted annualized HIV-1 incidence was 2.5% (2.0-3.0), whereas NAAT-based incidence was of 2.6%. In addition, LAg-based incidence in men (1.8%; 1.2-2.5) and women (3.2%; 2.4-3.9) were similar to estimates based on observed incidence (men = 1.7%, women = 3.1%). Changes in HIV-1 incidence with age in men and women further validate plausibility of the algorithm. These results demonstrate that the LAg EIA, in a serial algorithm with VL, is a cost-effective tool to estimate HIV-1 incidence in cross-sectional surveys.

Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring.

Scaling up access to HIV viral load testing for individuals undergoing antiretroviral therapy in low-resource settings is a global health priority, as emphasised by research showing the benefits of suppressed viral load for the individual and the whole population. Historically, large-scale diagnostic test implementation has been slow and incomplete because of service delivery and other challenges. Building on lessons from the past, in this Personal View we propose a new framework to accelerate viral load scale-up and ensure equitable access to this essential test. The framework includes the following steps: (1) ensuring adequate financial investment in scaling up this test; (2) achieving pricing agreements and consolidating procurement to lower prices of the test; (3) strengthening functional tiered laboratory networks and systems to expand access to reliable, high-quality testing across countries; (4) strengthening national leadership, with prioritisation of laboratory services; and (5) demand creation and uptake of test results by clinicians, nurses, and patients, which will be vital in ensuring viral load tests are appropriately used to improve the quality of care. The use of dried blood spots to stabilise and ship samples from clinics to laboratories, and the use of point-of-care diagnostic tests, will also be important for ensuring access, especially in settings with reduced laboratory capacity. For countries that have just started to scale up viral load testing, lessons can be learnt from countries such as Botswana, Brazil, South Africa, and Thailand, which have already established viral load programmes. This framework might be useful for guiding the implementation of viral load with the aim of achieving the new global HIV 90-90-90 goals by 2020.

Strengthening the Tuberculosis Specimen Referral Network in Uganda: The Role of Public-Private Partnerships.

BACKGROUND: Diagnosis of multidrug-resistant tuberculosis and prompt initiation of effective treatment rely on access to rapid and reliable drug-susceptibility testing. Efficient specimen transport systems and appropriate training on specimen referral contribute to optimal and timely access to tuberculosis diagnostic services. METHODS: With support and technical assistance from a public-private partnership (PPP) between Becton Dickinson and the US President's Emergency Plan for AIDS Relief, the Uganda National TB Reference Laboratory (NTRL) and National TB and Leprosy Program redesigned the tuberculosis specimen transport network and trained healthcare workers with the goal of improving multidrug-resistant tuberculosis detection. RESULTS: Between 2008 and 2011, the PPP mapped 93% of health facilities and trained 724 healthcare and postal staff members covering 72% of districts. Strengthening the tuberculosis specimen referral system increased referrals from presumptive multidrug-resistant tuberculosis cases by >10-fold, with 94% of specimens reaching the NTRL within the established target transport time. CONCLUSIONS: This study demonstrates the potential of PPP collaborations with ministries of health to positively influence patient care by strengthening laboratory systems through increased access to drug-susceptibility testing in Uganda. Ongoing efforts to integrate specimen transport networks will maximize resources and improve patient management.

Ensuring quality: a key consideration in scaling-up HIV-related point-of-care testing programs.

OBJECTIVE: The objective of the WHO/US President's Emergency Plan for AIDS Relief consultation was to discuss innovative strategies, offer guidance, and develop a comprehensive policy framework for implementing quality-assured HIV-related point-of-care testing (POCT). METHODS: The consultation was attended by representatives from international agencies (WHO, UNICEF, UNITAID, Clinton Health Access Initiative), United States Agency for International Development, Centers for Disease Control and Prevention/President's Emergency Plan for AIDS Relief Cooperative Agreement Partners, and experts from more than 25 countries, including policy makers, clinicians, laboratory experts, and program implementers. MAIN OUTCOMES: There was strong consensus among all participants that ensuring access to quality of POCT represents one of the key challenges for the success of HIV prevention, treatment, and care programs. The following four strategies were recommended: implement a newly proposed concept of a sustainable quality assurance cycle that includes careful planning; definition of goals and targets; timely implementation; continuous monitoring; improvements and adjustments, where necessary; and a detailed evaluation; the importance of supporting a cadre of workers [e.g. volunteer quality corps (Q-Corps)] with the role to ensure that the quality assurance cycle is followed and sustained; implementation of the new strategy should be seen as a step-wise process, supported by development of appropriate policies and tools; and joint partnership under the leadership of the ministries of health to ensure sustainability of implementing novel approaches. CONCLUSION: The outcomes of this consultation have been well received by program implementers in the field. The recommendations also laid the groundwork for developing key policy and quality documents for the implementation of HIV-related POCT.

Access and Quality of HIV-Related Point-of-Care Diagnostic Testing in Global Health Programs.

Access to point-of-care testing (POCT) improves patient care, especially in resource-limited settings where laboratory infrastructure is poor and the bulk of the population lives in rural settings. However, because of challenges in rolling out the technology and weak quality assurance measures, the promise of human immunodeficiency virus (HIV)-related POCT in resource-limited settings has not been fully exploited to improve patient care and impact public health. Because of these challenges, the Joint United Nations Programme on HIV/AIDS (UNAIDS), in partnership with other organizations, recently launched the Diagnostics Access Initiative. Expanding HIV programs, including the "test and treat" strategies and the newly established UNAIDS 90-90-90 targets, will require increased access to reliable and accurate POCT results. In this review, we examine various components that could improve access and uptake of quality-assured POC tests to ensure coverage and public health impact. These components include evaluation, policy, regulation, and innovative approaches to strengthen the quality of POCT.

Generation of dried tube specimen for HIV-1 viral load proficiency test panels: a cost-effective alternative for external quality assessment programs.

Participation in external quality assessment programs is critical to ensure quality clinical laboratory testing. Commercially available proficiency test panels for HIV-1 virus load testing that are used commonly in external quality assessment programs remain a financial obstacle to resource-limited countries. Maintaining cold-chain transportation largely contributes to the cost of traditional liquid proficiency test panels. Therefore, we developed and evaluated a proficiency test panel using dried tube specimens that can be shipped and stored at ambient temperature. This dried tube specimens panel consisted of 20 µl aliquots of a HIV-1 stock that were added to 2 ml tubes and left uncapped for drying, as a preservation method. The stability of dried tube specimens at concentrations ranging from 10² to 106·5 RNA copies/ml was tested at different temperatures over time, showing no viral load reduction at 37 °C and a decrease in viral load smaller than 0.5 Log10 at 45 °C for up to eight weeks when compared to initial results. Eight cycles of freezing-thawing had no effect on the stability of the dried tube specimens. Comparable viral load results were observed when dried tube specimen panels were tested on Roche CAPTAQ, Abbott m2000, and Biomerieux easyMAG viral load systems. Preliminary test results of dried proficiency test panels shipped to four African countries at ambient temperature demonstrated a low inter assay variation (SD range: 0.29-0.41 Log10 RNA copies/ml). These results indicated that HIV-1 proficiency test panels generated by this methodology might be an acceptable alternative for laboratories in resource-limited countries to participate in external quality assessment programs.

Laboratory equipment maintenance: a critical bottleneck for strengthening health systems in sub-Saharan Africa?

Properly functioning laboratory equipment is a critical component for strengthening health systems in developing countries. The laboratory can be an entry point to improve population health and care of individuals for targeted diseases - prevention, care, and treatment of TB, HIV/AIDS, and malaria, plus maternal and neonatal health - as well as those lacking specific attention and funding. We review the benefits and persistent challenges associated with sustaining laboratory equipment maintenance. We propose equipment management policies as well as a comprehensive equipment maintenance strategy that would involve equipment manufacturers and strengthen local capacity through pre-service training of biomedical engineers. Strong country leadership and commitment are needed to assure development and sustained implementation of policies and strategies for standardization of equipment, and regulation of its procurement, donation, disposal, and replacement.

Dried tube specimens: a simple and cost-effective method for preparation of HIV proficiency testing panels and quality control materials for use in resource-limited settings.

HIV testing has rapidly expanded worldwide, but proficiency testing (PT) programs to monitor and improve the quality of testing are often lacking in resource-limited settings (RLS). Traditional PT programs and quality control reagents use serum or plasma specimens requiring stringent conditions for storage and transportation. A novel, simple and easy to use approach, based on dried tube specimens (DTS), was developed that can help monitor the quality of HIV antibody testing in RLS. DTS were prepared by drying 20 microl of specimen overnight at room temperature. The addition of a green dye (0.1%) made the DTS pellets visible without affecting the test results. Before testing, the DTS were rehydrated with 200 microl of PBS-Tween buffer. A panel of 303 DTS samples (135 HIV positive and 168 HIV negative) was evaluated with two rapid tests. Sensitivity and specificity with the Determine HIV-1/2 test were 99.3% and 99.4%, respectively, and with OraQuick were 98.5% and 100%, respectively. Stability studies showed that HIV-specific antibodies in the DTS specimens were stable at 4 degrees C and 25 degrees C for 4 weeks, with only marginal decline at 37 degrees C and 45 degrees C over 4 weeks. The DTS-based PT program was piloted successfully in 24 testing sites in Kenya. Results demonstrate that the DTS is a simple to use, practical method to prepare and distribute PT panels and quality control specimens to monitor HIV testing practices in RLS.

Laboratory challenges in the scaling up of HIV, TB, and malaria programs: The interaction of health and laboratory systems, clinical research, and service delivery.

Strengthening national health laboratory systems in resource-poor countries is critical to meeting the United Nations Millennium Development Goals. Despite strong commitment from the international community to fight major infectious diseases, weak laboratory infrastructure remains a huge rate-limiting step. Some major challenges facing laboratory systems in resource-poor settings include dilapidated infrastructure; lack of human capacity, laboratory policies, and strategic plans; and limited synergies between clinical and research laboratories. Together, these factors compromise the quality of test results and impact patient management. With increased funding, the target of laboratory strengthening efforts in resource-poor countries should be the integrating of laboratory services across major diseases to leverage resources with respect to physical infrastructure; types of assays; supply chain management of reagents and equipment; and maintenance of equipment.

Current HIV-2 diagnostic strategy overestimates HIV-2 prevalence in China.

A significant number of HIV-2 infections have been reported in China using Western blot as per current guidelines for HIV-2 diagnosis in China. However, most specimens were also positive on HIV-1 Western blot suggesting cross-reactivity and possible overestimation. We carried out the current study to evaluate a strategy to diagnose the HIV-2 infections in China. A total of 119 specimens received from 16 provinces were likely to be HIV-2 when tested according to current guidelines in China using the Genelabs Western blot (HIV Blot 2.2 WB). Further testing by HIV-2 WB (Bio-Rad New LAV Blot II or Genelabs HIV Blot 1.2 WB) scored 56 (47.1%) of 119 samples with banding pattern suggestive of HIV-2 infection, and 63 (52.9%) were HIV-2 indeterminate. A peptide-based HIV-1 and HIV-2 enzyme immunoassay for differential diagnosis of HIV-1 and HIV-2 infections was validated and used. This in-house EIA demonstrated that only 1 (0.8%) of 119 specimens had HIV-2 specific antibodies, while 2 (1.7%) were dually reactive. These results were highly concordant (>99%) with those by Inno-LIA HIV-I/II (Innogenetics, Belgium), which also use specific peptides for type-specific diagnosis. Our data demonstrates that HIV-2 infection is rare in China, and HIV-2 Western blot may overestimate the prevalence of HIV-2 in the population with HIV-1. The HIV-2 diagnostic strategy in China needs to be revised to include more specific peptide-based immunoassays.

The most efficient use of resources to identify those in need of antiretroviral treatment in Africa: empirical data from Côte d'Ivoire's Drug Access Initiative.

OBJECTIVE: To describe the cost and outcome associated with the use of CD4 cell count and viral load tests as part of screening strategies to identify persons eligible for subsidized antiretroviral therapy (ART) in Côte d'Ivoire. METHODS: Empirical data from the Drug Access Initiative in Côte d'Ivoire (DAI-CI) were used to describe the laboratory cost of patient screening using sequential clinical staging, CD4 cell count, and viral load and the proportion of screened patients identified as eligible for ART. We also estimated costs modelling a parallel screening algorithm, across a range of laboratory costs and with current international recommendations to assess treatment eligibility. Benefit was defined as being found eligible for ART. RESULTS: Of the 2138 HIV-positive, ART-naive, adults who presented to the DAI-CI between July 1998 and July 2000, median CD4 cell count was 172 x 10(6) cells/microl. DAI-CI criteria identified 2057 (96%) of these persons eligible for antiretroviral treatment. In a serial screening algorithm, 75% were eligible by CDC clinical stage B or C; 18% by CD4 cell count less than 500 x 10(6) cells/microl; and an estimated 3.9% by a viral load greater than 10 000 copies/ml. Use of the current US recommendations and a serial algorithm would have resulted in 1977 (92%) persons eligible for ART: 75% by CDC clinical stage B or C; 15% by CD4 cell count less than 350 x 10(6) cells/microl (including 8% < 200 x 10(6) cells/microl); and an estimated 3.6% due to viral load greater than 55 000 copies/ml. Using DAI-CI criteria and heavily subsidized laboratory test costs, the addition of CD4 cell count to clinical criteria cost US dollar 50 (serial algorithm) and US dollar 203 (parallel algorithm) to identify each additional eligible person. Modelling current recommendations with a serial algorithm, CD4 cell count cost an average US dollar 62/eligible person (US recommendations) and US dollar 109 (WHO recommendations). The addition of viral load cost between US dollar 108 (serial algorithm DAI) to US dollar 1700 (parallel algorithm DAI) to identify each additional eligible person. CONCLUSION: In the African context of scarce resources and the huge unmet demands for voluntary HIV testing and for ART, simple screening strategies are needed to identify those most in need of ART. Health personnel should be trained to identify and refer clinically symptomatic persons. Viral load testing is of high cost and dubious benefit and should not be part of screening algorithms for initiating ART.