Mortality during and following hospital admission among school-aged children: a cohort study.

Background: Far less is known about the reasons for hospitalization or mortality during and after hospitalization among school-aged children than among under-fives in low- and middle-income countries. This study aimed to describe common types of illness causing hospitalisation; inpatient mortality and post-discharge mortality among school-age children at Kilifi County Hospital (KCH), Kenya. Methods: A retrospective cohort study of children 5-12 years old admitted at KCH, 2007 to 2016, and resident within the Kilifi Health Demographic Surveillance System (KHDSS). Children discharged alive were followed up for one year by quarterly census. Outcomes were inpatient and one-year post-discharge mortality. Results: We included 3,907 admissions among 3,196 children with a median age of 7 years 8 months (IQR 74-116 months). Severe anaemia (792, 20%), malaria (749, 19%), sickle cell disease (408, 10%), trauma (408, 10%), and severe pneumonia (340, 8.7%) were the commonest reasons for admission. Comorbidities included 623 (16%) with severe wasting, 386 (10%) with severe stunting, 90 (2.3%) with oedematous malnutrition and 194 (5.0%) with HIV infection. 132 (3.4%) children died during hospitalisation. Inpatient death was associated with signs of disease severity, age, bacteraemia, HIV infection and severe stunting. After discharge, 89/2,997 (3.0%) children died within one year during 2,853 child-years observed (31.2 deaths [95%CI, 25.3-38.4] per 1,000 child-years). 63/89 (71%) of post-discharge deaths occurred within three months and 45% of deaths occurred outside hospital. Post-discharge mortality was positively associated with weak pulse, tachypnoea, severe anaemia, HIV infection and severe wasting and negatively associated with malaria.  Conclusions: Reasons for admissions are markedly different from those reported in under-fives. There was significant post-discharge mortality, suggesting hospitalisation is a marker of risk in this population. Our findings inform guideline development to include risk stratification, targeted post-discharge care and facilitate access to healthcare to improve survival in the early months post-discharge in school-aged children.

Global selection of Plasmodium falciparum virulence antigen expression by host antibodies.

Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity.

Memory B cells are a more reliable archive for historical antimalarial responses than plasma antibodies in no-longer exposed children.

Humans respond to foreign antigen by generating plasma Abs and memory B cells (MBCs). The Ab response then declines, sometimes to below the limit of detection. In contrast, MBCs are generally thought to be long-lived. We tested and compared Plasmodium falciparum (Pf)-specific Ab and MBC responses in two populations of children: (i) previously exposed children who had documented Pf infections several years ago, but minimal exposure since then; and (ii) persistently exposed children living in a separate but nearby endemic area. We found that although Pf-specific plasma Abs were lower in previously exposed children compared with persistently exposed children, their cognate MBCs were maintained at similar frequencies. We conclude that serological analysis by itself would greatly underestimate the true memory of Pf-specific Ab responses in previously exposed children living in areas where Pf transmission has been reduced or eliminated.