Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults.

BACKGROUNDSanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODSThis randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV-) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/µL). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later.RESULTSThere were no solicited adverse events in the 9 HIV- and 12 HIV+ participants. After CHMI, 6 of 6 NS controls, 1 of 5 HIV- vaccinees, and 4 of 4 HIV+ vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ CD4+ T cell responses, and Vδ2+ γδ CD3+ T cells were nonsignificantly higher in HIV- than in HIV+ vaccinees. Sera from HIV- vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fcγ3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies.CONCLUSIONSPfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa.TRIAL REGISTRATIONClinicalTrials.gov NCT03420053.FUNDINGEquatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354-01.

Assessment of the WHO non-communicable diseases kit for humanitarian emergencies in South Sudan: a retrospective, prospective, observational study.

BACKGROUND: The WHO Non-Communicable Diseases Kit (NCDK) was developed to support care for non-communicable diseases (NCDs) in humanitarian settings. Targeting primary healthcare, each kit contains medicines and supplies that are forecasted to meet the needs of 10,000 people for 3 months. This study aimed to evaluate the NCDK deployment process, contents, usage and limitations, and to explore its acceptability and effectiveness among healthcare workers (HCWs) in South Sudan. METHODS: This mixed-method observational study captured data from pre-and-post NCDK deployment. Six data collection tools included: (i) contextual analysis, (ii) semi-structured interviews, in addition to surveys measuring/assessing (iii) healthcare workers' knowledge about NCDs, and healthcare workers' perceptions of: (iv) health facility infrastructure, (v) pharmaceutical supply chain, and (vi) NCDK content. The pre- and post-deployment evaluations were conducted in four facilities (October-2019) and three facilities (April-2021), respectively. Descriptive statistics were used for quantitative data and content analysis for open-ended questions. A thematic analysis was applied on interviews findings and further categorized into four predetermined themes. RESULTS: Compared to baseline, two of the re-assessed facilities had improved service availability for NCDs. Respondents described NCDs as a growing problem that is not addressed at a national level. After deployment, the same struggles were intensified with the COVID-19 pandemic. The delivery process was slow and faced delays associated with several barriers. After deployment, poor communications and the "push system" of inventories were commonly perceived by stakeholders, leading to expiry/disposal of some contents. Despite being out-of-stock at baseline, at least 55% of medicines were found to be unused post-deployment and the knowledge surveys demonstrated a need for improving HCWs knowledge of NCDs. CONCLUSIONS: This assessment further confirmed the NCDK role in maintaining continuity of care on a short-term period. However, its effectiveness was dependent on the health system supply chain in place and the capacity of facilities to manage and treat NCDs. Availability of medicines from alternative sources made some of the NCDK medicines redundant or unnecessary for some health facilities. Several learnings were identified in this assessment, highlighting barriers that contributed to the kit underutilization.