Immunoparesis and Outcome in Measles

Coovadia, Hoosen; Brain, Peter; Hallett, A. F.; Wesley, A. G.; Henderson, L; Vos, G. H.

doi:10.1016/s0140-6736(77)92056-6

Cited by 33 publications

(12 citation statements)

References 5 publications

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“…Profound lymphopenia has previously been associated with severe measles and high mortality in African children (22,23,45), and the four children in our study who died during hospitalization had lymphocyte counts in the lowest quartile at study entry. More profound decreases in T-cell counts during acute measles have also been associated with malnutrition (24), and the acutely malnourished (wasted) children enrolled in our study had lymphocyte counts lower than those of children who were not wasted.…”

Section: Discussionsupporting

confidence: 51%

Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles

Ryon

Moss

Monze

et al. 2002

Clin Vaccine Immunol

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Measles is associated with immunosuppression and increased susceptibility to secondary infections and is a particular problem in developing countries. Lymphocyte changes accompanying immune activation and regulation of the immune response may contribute to immunosuppression. To evaluate lymphocyte changes during measles, children (n ‫؍‬ 274) hospitalized with measles in Lusaka, Zambia, were evaluated at entry, discharge, and 1-month follow-up and compared to healthy Zambian children (n ‫؍‬ 98). Lymphopenia was present on hospital admission and reflected decreased CD4 and CD8 T cells but resolved quickly. Lymphopenia was most marked in girls, in those with temperatures of >38.5°C, and in malnourished children. CD4/CD8 ratios were decreased at all time points and were lower in boys than in girls at discharge and follow-up. Spontaneous death occurred in cultured lymphocytes, and the proportions of freshly isolated cells undergoing apoptosis, based on annexin V and propidium iodide staining, were increased. Surface Fas was increased on both CD4 and CD8 T cells compared to controls, and expression was greater on CD4 T cells and was inversely correlated with lymphocyte viability in culture at study entry. Mitogen stimulation of lymphocytes improved viability, but inhibitors of Fas, tumor necrosis factor (TNF)-related apoptosis-inducing ligand, and TNF did not. Plasma levels of ␤ 2 microglobulin and soluble Fas, Fas ligand, CD8, CD4, and TNF receptor were increased, and soluble CD8 was higher in boys than in girls. The multiple effects of measles on lymphocytes from Zambian children include decreased numbers in circulation, increased activation, and increased susceptibility to cell death, with substantive differences in the magnitude of these changes between boys and girls.Measles causes nearly 1 million deaths per year worldwide, with the heaviest burden occurring in sub-Saharan Africa (9). The high morbidity and mortality associated with measles virus (MV) infection is due primarily to secondary infections, particularly of the respiratory and gastrointestinal tracts (12,53,55). Increased susceptibility to other infectious diseases has been linked to the immune suppression associated with this infection. Cell-mediated immunity, manifested by decreased delayed-type hypersensitivity responses to skin test antigens and decreased proliferation of lymphocytes after stimulation in vitro, is suppressed, and this suppression may persist for several months after recovery (74,80,86,87).The mechanism of MV-induced immune suppression is incompletely understood, and few studies of children in developing countries, where mortality rates are highest, have been done. Lymphocyte activation is a consistent feature of acute measles (34, 38) in North and South American children, and we have proposed that the observed cytokine "shift" from type 1 cytokines early during infection to type 2 cytokines during and after recovery (35) inhibits development of effective type 1 cytokine-mediated cell-mediated immunity responses upon subsequent exp...

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Section: Discussionsupporting

confidence: 51%

Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles

Ryon

Moss

Monze

et al. 2002

Clin Vaccine Immunol

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“…There appears to be an important link between lymphocyte numbers and the immediate and late complications of certain neoplastic and infectious diseases (Papatestas and Kark, 1974;Coovadia et al, 1977;Jackson et al, 1977). Profound lymphopenia (<2000/mm3; <2 -0 x 109/1) during the exanthem in measles, generally distinguishes children who will die or develop chronic chest disease from those who will recover (Coovadia et al, 1977).…”

mentioning

confidence: 99%

Immunological events in acute measles influencing outcome.

Coovadia¹,

Wesley²,

Brain³

1978

Arch Dis Child

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77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.

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“…Although all the children recovered and their infection was considered mild, it is likely that the antigen load was not similar in the two groups. Coovadia et al [8] have reported recently that mortality in measles is highest in chil dren who have severe immunodépression; they found that the children who died had marked lymphopaenia and although the proportion of T and B lymphocytes was normal, their numbers were depressed com pared to both the children who survived and the healthy controls. The depression of T lymphocytes could be another reason for the lack of migration inhibition.…”

Section: Discussionmentioning

confidence: 98%

“…It has always been an enigma as to why some children with mea sles and not others are prone to tuberculo sis. It has been reported recently that a vig orous cell-mediated immune response is necessary to restrict the spread of tuberculo sis [2], This may be relevant to measles be cause a number of workers using intradermal [3,4], leucocyte migration [5], lymphocyte transformation [6,7] and other tests [8] have investigated the cell-mediated response and some have found it to be impaired dur ing and for a variable period after measles. Nordal et al [5] used measles virus as anti gen in the leucocyte migration test and won dered whether measles-virus-induced migra tion inhibition was an immunologically un specific phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Cell-Mediated Immunity in Measles Using the Leucocyte Migration Test

Desai¹,

Strashoon²,

Wesley³

1978

Int Arch Allergy Immunol

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The cell-mediated immune response was investigated in 21 children with acute measles and in 8 healthy children using the intradermal Heaf and leucocyte migration tests. Tuberculin and purified protein derivative were used as antigens. Whereas all the children with measles were anergic in the in vivo test, two groups of children, i. e. ‘reactors’ and ‘non-reactors’ could be delineated with the in vitro test. The mechanisms responsible for the anergy are discussed.

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Immunoparesis and Outcome in Measles

Cited by 33 publications

References 5 publications

Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles

Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles

Immunological events in acute measles influencing outcome.

Cell-Mediated Immunity in Measles Using the Leucocyte Migration Test

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