HIV-associated dementia (HAD) has received little attention in sub-Saharan Africa, and there are no data available from Malawi. We used the International HIV Dementia Scale (IHDS), a cross-cultural, simple and validated screening tool to study the prevalence of suspected HAD, defined as an IHDS score

Pregnancy-associated Plasmodium falciparum infection impacts the health of mothers and newborns, but little is known about the effects of these infections on infant susceptibility to malaria. We followed 473 mother-infant pairs during pregnancy and through 2 years of age. We observed that children born to mothers with placental malaria, but not those born to mothers with peripheral infection without evidence of placental sequestration, had increased risk of malaria during the first year of life compared with children born to mothers with no malaria during pregnancy. Malaria infections with placental sequestration have long-lasting impact on infant susceptibility to malaria infection.

US National Institutes of Health.

Conducting clinical trials to prevent and treat infectious diseases in pregnancy is essential to saving maternal and newborn lives, though it is fraught with challenges. We have been conducting research in malaria treatment and prevention in children and pregnant women in Blantyre, Malawi for over a decade. Here, we review some of the unique challenges that we have faced in leading research studies that with rigor and integrity and maintaining the highest ethical standard. We conclude with concrete strategies to overcome some of the apparent obstacles that frequently focus on building trust through bidirectional communication with local health workers and communities. We also highlight the key role of local and international investigators to advocate for the health of the communities in which they work.

A successful pregnancy depends on the maintenance of tolerance at the fetal–maternal interface; strong inflammation in the placental bed is generally associated with adverse fetal outcomes. Among the mechanisms that foster tolerance and limit inflammation, the fetal immune system favors Th2 or regulatory responses over Th1 responses. The unintended consequence of this functional program is high susceptibility to infections. Human Vδ2 T cells mount innate-like responses to a broad range of microorganisms and are poised for Th1 responses before birth. In infants they likely play a key role in protection against pathogens by exerting early Th1 effector functions, improving function of other innate cells, and promoting Th1 polarization of adaptive responses. However, their propensity to release Th1 mediators may require careful regulation during fetal life to avoid exaggerated proinflammatory responses. We investigated molecules with the potential to act as a rheostat for fetal Vδ2 cells. Programmed death 1 (PD1) is a negative regulator of T cell responses and a determinant of tolerance, particularly at the fetal–maternal interface. Neonatal Vδ2 cells upregulate PD1 shortly after activation and, unlike their adult counterparts, express this molecule for at least 28 d. Engagement of PD1 by one of its ligands, PDL1, effectively dampens TCR-mediated responses (TNF-α production and degranulation) by neonatal Vδ2 cells and may thus help maintain their activity within safe limits. PD1 expression by neonatal Vδ2 cells is inversely associated with promoter DNA methylation. Prolonged PD1 expression may be part of a functional program to control Vδ2 cell inflammatory responses during fetal life.

Background Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa. Graphic abstract

To update the landscape analysis of vaccine injuries no-fault compensation programmes, we conducted a scoping review and a survey of World Health Organization Member States. We describe the characteristics of existing no-fault compensation systems during 2018 based on six common programme elements. No-fault compensation systems for vaccine injuries have been developed in a few high-income countries for more than 50 years. Twenty-five jurisdictions were identified with no-fault compensation programmes, of which two were recently implemented in a low-and a lower-middle-income country. The no-fault compensation programmes in most jurisdictions are implemented at the central or federal government level and are government funded. Eligibility criteria for vaccine injury compensation vary considerably across the evaluated programmes. Notably, most programmes cover injuries arising from vaccines that are registered in the country and are recommended by authorities for routine use in children, pregnant women, adults (e.g. influenza vaccines) and for special indications. A claim process is initiated once the injured party or their legal representative files for compensation with a special administrative body in most programmes. All no-fault compensation programmes reviewed require standard of proof showing a causal association between vaccination and injury. Once a final decision has been reached, claimants are compensated with either: lump-sums; amounts calculated based on medical care costs and expenses, loss of earnings or earning capacity; or monetary compensation calculated based on pain and suffering, emotional distress, permanent impairment or loss of function; or combination of those. In most jurisdictions, vaccine injury claimants have the right to seek damages either through civil litigation or from a compensation scheme but not both simultaneously. Data from this report provide an empirical basis on which global guidance for implementing such schemes could be developed.

A simple score incorporating age, ART duration and adherence, and CD4 count can accurately identify adults at low risk for VF in a sub-Saharan African setting. In areas with high ART utilisation and limited VL testing capacity, a targeted approach could optimise routine VL monitoring while identifying adults in need of alternate ART regimens.