A Quality Management Approach to Implementing Point-of-Care Technologies for HIV Diagnosis and Monitoring in Sub-Saharan Africa

Technology advances in rapid diagnosis and clinical monitoring of human immunodeficiency virus (HIV) infection have been made in recent years, greatly benefiting those at risk of HIV infection, those needing care and treatment, and those on antiretroviral (ART) therapy in sub-Saharan Africa. However, resource-limited, geographically remote, and harsh climate regions lack uniform access to these technologies. HIV rapid diagnostic tests (RDTs) and monitoring tools, such as those for CD4 counts, as well as tests for coinfections, are being developed and have great promise in these settings to aid in patient care. Here we explore the advances in point-of-care (POC) technology in the era where portable devices are bringing the laboratory to the patient. Quality management approaches will be imperative for the successful implementation of POC testing in endemic settings to improve patient care

Towards a comprehensive research and development plan to support the control, elimination and eradication of neglected tropical diseases.

To maximise the likelihood of success, global health programmes need repeated, honest appraisal of their own weaknesses, with research undertaken to address any identified gaps. There is still much to be learned to optimise work against neglected tropical diseases. To facilitate that learning, a comprehensive research and development plan is required. Here, we discuss how such a plan might be developed

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection

Utility of a Point-of-Care Malaria Rapid Diagnostic Test for Excluding Malaria as the Cause of Fever among HIV-Positive Adults in Rural Rakai, Uganda

We compared results of a malaria rapid diagnostic test (Binax Now® Malaria, Binax-M, Inverness Medical Innovations, Inc., Waltham, MA) performed at rural mobile clinics in Uganda by clinicians evaluating febrile adult HIV patients to thick smear evaluated at a central laboratory by trained microscopists. Two hundred forty-six samples were analyzed, including 14 (5.7%) which were thick-smear positive for falciparum malaria. Sensitivity of Binax-M compared with thick smear was 85.7% (95% CI: 57.2–98.2), specificity 97.8% (95% CI: 94.9–99.3), positive and negative predictive values were 70.6% (95% CI: 44.0–89.7) and 99.1% (95% CI: 96.8–99.9), respectively. The rapid diagnostic test accurately ruled malaria “in or out” at the point-of-care, facilitating appropriate clinical management and averting unnecessary anti-malarial therapy

CD4 Stabilization Tubes Provide Improved Accuracy of Absolute CD4 T-Cell Counts Compared to Standard K3 EDTA Tubes in Human Immunodeficiency Virus Immunologic Monitoring in Resource-Poor Settings▿

CD4 stabilization tubes have the ability to ensure internal quality control in the human immunodeficiency virus (HIV) monitoring laboratory by maintaining accurate absolute CD4 T-cell counts for up to 6 days. Here, we assessed this technology for its use in an HIV clinical monitoring laboratory in a resource-poor setting in rural Uganda

Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice

Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluatio