Dataset Information

Gradual acquisition of immunity to severe malaria with increasing exposure.

ABSTRACT: Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly. We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission settings in Tanzania, combined with data from several African countries on the age distribution and overall incidence of severe malaria. We found that immunity to severe disease was acquired more gradually with exposure than previously thought. The model also suggests that physiological changes, rather than exposure, may alter the symptoms of disease with increasing age, suggesting that a later age at infection would be associated with a higher proportion of cases presenting with cerebral malaria regardless of exposure. This has consequences for the expected pattern of severe disease as transmission changes. Careful monitoring of the decline in immunity associated with reduced transmission will therefore be needed to ensure rebound epidemics of severe and fatal malaria are avoided.

SUBMITTER: Griffin JT

PROVIDER: S-EPMC4309004 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gradual acquisition of immunity to severe malaria with increasing exposure.

Griffin Jamie T JT Hollingsworth T Déirdre TD Reyburn Hugh H Drakeley Chris J CJ Riley Eleanor M EM Ghani Azra C AC

Proceedings. Biological sciences 20150201 1801

Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly. We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission sett ...[more]

PMID: 25567652

Similar Datasets

Project description:Background: Going without sleep for long periods of time can produce a range of experiences, including perceptual distortions and hallucinations. Many questions, however, remain unanswered regarding the types of symptoms which are most reliably elicited, the time of symptom onset, and whether symptoms worsen over time toward psychotic decompensation. Since sleep deprivation exceeding 48 h is considered unethical today, an examination of historical studies with extreme sleep-loss duration is needed to obtain information about what happens during prolonged sleep loss. Methods: A systematic-review approach was used to identify experimental and observational studies of sleep deprivation in healthy people which describe the effects of prolonged sleep loss on psychopathological symptoms, without any date restriction. Results: A total of 476 articles were identified. Of these, 21 were eligible for inclusion. Duration of sleep loss ranged between 24 h and 11 nights (total 760 participants; average 72-92 h without sleep). All studies except one reported perceptual changes, including visual distortions (i.e., metamorphopsias), illusions, somatosensory changes and, in some cases, frank hallucinations. The visual modality was the most consistently affected (in 90% of the studies), followed by the somatosensory (52%) and auditory (33%) modalities. Symptoms rapidly developed after one night without sleep, progressing in an almost fixed time-dependent way. Perceptual distortions, anxiety, irritability, depersonalization, and temporal disorientation started within 24-48 h of sleep loss, followed by complex hallucinations and disordered thinking after 48-90 h, and delusions after 72 h, after which time the clinical picture resembled that of acute psychosis or toxic delirium. By the third day without sleep, hallucinations in all three sensory modalities were reported. A period of normal sleep served to resolve psychotic symptoms in many-although not all-cases. Conclusions: Psychotic symptoms develop with increasing time awake, from simple visual/somatosensory misperceptions to hallucinations and delusions, ending in a condition resembling acute psychosis. These experiences are likely to resolve after a period of sleep, although more information is required to identify factors which can contribute to the prevention of persistent symptoms.

Project description:Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways ("immunity functions"): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.

Project description:Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

Dataset Information

Gradual acquisition of immunity to severe malaria with increasing exposure.

Publications

Gradual acquisition of immunity to severe malaria with increasing exposure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets