Impaired neutralizing activity by transplacental measles antibodies in infants born to HIV-1-infected mothers.

AIM: Growing numbers of newborns are saved from HIV infection through increased access to mother-to-child transmission prevention programmes. The maternally derived humoral immunity of these children might be impaired, both in terms of quantity and in terms of quality, with consequences for the timing of immunization against measles. METHODS: A cell-ELISA technique compared the neutralizing activity on Edmonston strain measles virus of sera from 1- to 4-month-old infants. Ten serum specimens came from noninfected infants of HIV-infected mothers and another 10 from infants of healthy mothers. The sera were matched for the level of conventional ELISA measles antibodies. RESULTS: Reflecting infection of the Vero cells by non-neutralized virus, optical density values were significantly higher for the sera from the children of the HIV-infected mothers than for those of the noninfected mothers (p < 0.001). CONCLUSION: Maternally derived protection against measles may be impaired by the mother's HIV infection, relating to the quality rather than to the quantity of transplacental antibodies. Selective, early immunization with live attenuated measles vaccine should be evaluated in noninfected children of HIV-1-infected mothers.

Anthropometry and subsequent mortality in groups of children aged 6-59 months in Guinea-Bissau.

To assess the importance of nutritional status for subsequent survival, 2228 children aged 6-59 mo were followed for 8-12 mo in four different areas of Guinea-Bissau. The overall death rate was 0.62/100 child-months of follow-up (126 deaths) and 0.63 for the 1756 children who were examined on entering the study (109 deaths). Mortality was twice as high in the periurban as in the rural areas due to an outbreak of measles. In a bivariate analysis the relationship between nutritional status indicators and mortality was confounded by the age dependence of both. Using Cox's regression technique, height-for-age but not weight-for-height was positively correlated with survival. The number of children in the household was a better discriminator for death from measles than was nutritional status. Long-term factors, probably of multiple social origin, are likely causes of both relatively short stature and high mortality.

PIP: To assess the importance of nutritional status for subsequent survival, 2228 children aged 6-59 months were followed for 8-12 months in 4 different areas of Guinea-Bissau. The overall death rate was 0.62/100 child-months of follow-up (126 deaths) and 0.63 for the 1,756 children who were examined on entering the study (109 deaths). Mortality was twice as high in the rural areas due to an outbreak of measles. In a bivariate analysis the relationship between nutritional status indicators and mortality was confounded by the age dependence of both. Using Cox's regression technic, height-for-age but not weight-for age was positively correlated with survival. The number of children in a household was a better discriminator for death from measles than was nutritional status. Long-term factors, probably of multiple social origin, are likely causes of both relatively short stature and high mortality.

Determinants of delayed initiation of breastfeeding: a community and hospital study from Guinea-Bissau.

A prospective study on the timing of breastfeeding start in Bissau was undertaken in a periurban community (n = 734), and at the Central Hospital (n = 414). Only single, full-term, healthy children born by the vaginal route were included, the purpose being to characterize mothers who delay breastfeeding start for reasons not related to disease. Multivariate failure-time analysis (Cox' regression) was used to relate the child's age at breastfeeding start to a set of independent variables. In the community, those tending to delay breastfeeding start were mothers from the largest ethnic group in the country, mothers who had given birth at times other than the evening hours (6-12 pm) and mothers who had not attended antenatal clinics. At the hospital, delayed initiation was found among young mothers and mothers from one sparsely represented ethnic group. The most important determinant of delayed breastfeeding start was negative cultural ideas about colostrum.

PIP: In Guinea-Bissau, researchers analyzed January 1984-April 1986 data on 734 mother-infant pairs registered at health centers in the periurban settlement of Bandim and March 1984-May 1986 data on 414 mother-infant pairs at the maternity ward of the Hospital Simao Mendes in Bissau to determine when mothers begin breast feeding and learn determinants of delayed breast feeding. In Bandim, the most significant determinant of delaying breast feeding among mothers in the community study was being a member of the Balanta ethnic group, the largest technic group in the country (p=.0001). This may have been because the Balanta believe the colostrum harms the infant. Membership in the Mancanha ethnic group, the country's smallest, was a determinant of delayed breast feeding among the women in the hospital study (p=.0001). The researchers could not identify a reason for this effect among Mancanha women. Community mothers who delivered anytime before 6 pm and after midnight (p=.0001)especially between midnight and 5 am (p=.0002) and noon to 5 pm (p=.0354) tended to delay breast feeding. The 3rd determinant of delaying breast feeding among the women in the community study was no prenatal care (p=.0001). Prenatal care had no effect on delayed or early breast feeding among the women in the hospital study. Young maternal age (20 years) was another determinant of delayed breast feeding among the women in the hospital study (p=.0001). Women who delivered in 1985 in the hospital were more likely to initiate breast feeding early (p=.0001) but this was not the case in 1984 and 1986, however. Public health officials planned to sue these results to design and target education about the benefits of early initiation of breast feeding.

Phenotypic characterization of mononuclear white cells using finger-prick blood and light microscopy.

A technique for the enumeration of T cell subsets in capillary blood for use in the field is described. Mononuclear white cells were separated from 0.4 ml capillary blood, kept covered by culture medium on a Multitest slide, and incubated with monoclonal antibodies to the CD2, CD4, CD8, and interleukin-2 receptor antigens. Secondary and tertiary alkaline phosphatase conjugates were used for labeling. The substrate gave a distinct blue surface staining to the positive lymphocytes. Comparison was made with a conventional immunofluorescent antibody technique (r = 0.95).

Association between immune recognition of the malaria vaccine candidate antigen Pf155/RESA and resistance to clinical disease: a prospective study in a malaria-endemic region of west Africa.

We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide-binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity.

Child mortality in Stockholm during 1885-1910: the impact of household size and number of children in the family on the risk of death from measles.

Previous studies have associated overcrowding at the household level with increased mortality, especially from airborne diseases. This association may be confounded by associations with adverse socioeconomic conditions or low age at infection. This study investigated the effect of crowding on the risk of measles death. Individual entries in a population-based register and on death certificates for children aged 0-15 years living in one parish in Stockholm in 1885, 1891, and 1910 (n = 36,718) were used to analyze cause-specific and overall death rates in relation to household size and the number of children in the household, using Cox regression analysis. Bivariate analysis identified significant relations between crowding and the cause-specific risk of death, which were subsequently tested while controlling for other known risk factors for childhood death. Significant negative associations between crowding and the risk of death from pneumonia and bronchitis disappeared when controlling for other risk factors. A negative association between the risk of overall death and large household size became significantly positive when controlling for other risk factors. The increased risk of death from measles associated with proxies for crowding remained after controlling for other risk factors. In conclusion, crowding may have a statistically independent effect on the risk of death from measles.

Does age at the start of breast feeding influence infantile diarrhoea morbidity? A case-control study in periurban Guinea-Bissau.

Colostrum protects the newborn from intestinal infection by its content of secretory immunoglobulin A and other immediately acting factors. It may also induce maturation of the child's gastrointestinal immune defences, thus contributing to the protection against diarrhoeal disease later in infancy. To test this hypothesis, a case-control study on breast feeding and diarrhoea was carried out in a periurban community in Guinea-Bissau. The child's age at the start of breast feeding was ascertained soon after birth (n = 279). Subsequent cases of acute diarrhoea (n = 66) were identified at 3-monthly examinations, and four concurrent controls were randomly selected among attendants. Three separate estimates of association showed that the cases tended to have started breast feeding later after birth than the diarrhoea-free controls, but no single test was statistically significant. Early breast feeding might have consequences for diarrhoeal morbidity after the neonatal period.

A study on malaria infection during the acute stage of measles infection.

The recognized high mortality from measles in Africa is considered to be partly due to the flare-up of concomitant malaria infection. In 1987 there was a measles epidemic in the Rufiji Delta, Tanzania, in spite of recent vaccination campaigns. A comparative study was therefore conducted on the densities of malaria parasites in children during the acute stage of measles (67 consecutive cases, aged 5 months-19 years). The period of study was March-June, the peak season for malaria transmission. For each measles patient, a blood film was concomitantly taken from an asymptomatic age-matched child from the same village. Of 67 children with measles, 17 (25%) had parasitaemia ranging from 8 to 2480 parasites microliter-1 blood. Out of 67 asymptomatic control children 59 (88%) had parasitaemia ranging from 8 to 3400 parasites microliter-1 blood. This study indicates that malaria densities were lower during the acute stage of measles than in healthy children. The contribution of malaria to mortality in children with acute measles may be questioned.

Survival 0-6 years of age in a periurban community in Guinea-Bissau: a longitudinal assessment.

In the preparation of a child health-care project in a periurban settlement area with a population of 6200, a census identified 1464 children below 6 years of age. One thousand, one hundred and eighty-eight of these children were examined. They were followed up 12 months later, during which interval there was a current registration of the pregnancies, births and deaths in the area. The 360 newborns in the period were successively included in the follow-up. One hundred and forty-four deaths were documented, including the symptoms preceding their occurrence. Sixty-two of the deaths were due to epidemic measles. The probability of survival through the neonatal period was 0.941, to 12 months of age 0.803, and to 60 months 0.546. The health-work that ensued upon this study emphasizes intra-pregnancy care and immunizations to the young children.

Age at breast feeding start and postneonatal growth and survival.

Colostrum has important anti-infective properties. It may also somehow promote the development of the child's immunological system. Discarding colostrum, as practised in some cultures, could thus have adverse health consequences beyond the neonatal period. To test this hypothesis, the age at breast feeding start of 734 healthy newborns in urban Guinea-Bissau was ascertained. The children were then prospectively followed up to 3 years of age. Eighty nine deaths occurred during the study. The probability of death in the age interval 28 days to 3 years was about 20%. The child's age at breast feeding start had no statistical impact on postneonatal growth or survival. As a single measure, early breast feeding start is not likely to make much difference for the long term growth or survival of children living under material poverty conditions.

Nutritional status and measles: a community study in Guinea-Bissau.

In an urban settlement area with 6217 inhabitants, 1188 children of 0-71 months of age were weighed and measured in December 1978. Fourteen per cent of those more than nine months old were underweight for age. In February 1979 a measles epidemic started in the area and reached its peak in April. At least 236 of the children initially weighed caught the disease and 59 died of measles. Forty-nine of these had not been underweight in December 1978. In the age interval 9-35 months there was a tendency for measles death to be associated with a relatively low nutritional status. In a geographically-defined sub-population of the studied children, mean weight velocity from December to May was lower in those who had measles in the period than in those who did not contract it. The observations confirm the negative impact of measles on nutritional status. On the other hand, they question the supreme importance given to pre-existing malnutrition in explaining the high measles mortality in West African communities.

Sub-clinical cerebral oedema does not occur regularly during treatment for diabetic ketoacidosis.

Fulminant cerebral oedema is an uncommon, fatal complication of diabetic ketoacidosis (DKA) in children. This study aimed to find out whether the sub-clinical compression of the brain ventricles found by an earlier study, is a general phenomenon during intravenous treatment for DKA. Four boys and four girls were examined. Blood glucose values ranged from 40 to 24.6 mmol/l, base excess -34.6 to -13.6 and capillary blood pH 6.89-7.22. The patients received fluids containing both glucose and electrolytes, and insulin intravenously. After about 10h, blood glucose was 8.7-21.8 mmol/l and base excess had decreased substantially (-9.5 to -2.9) in seven of the eight cases. Computerized tomography of the brain was then performed, and again after full recovery. Only two of the patients had an initial decrease in intercaudate distance, which exceeded the variability found in a reference group. Compression of the cerebral ventricles does not occur regularly during treatment for DKA.

Selective compartmentalization of gammadelta-T lymphocytes in human breastmilk.

In human breastmilk, T lymphocytes with gammadelta-receptor (TCR) are more frequent than those with alphabeta-TCR, in comparison with peripheral blood. Differential representation has also been demonstrated for subpopulations of gammadelta-T cells. Reactivity was visualized with three monoclonal antibodies against Vdelta1, Vdelta2 and Vgamma2 on T cells from the breastmilk and peripheral blood of 12 women who had recently given birth. Confirming the results with Vdelta1, it was found that Vdelta1 (p < 0.01) and Vgamma2 (p < 0.05) but not Vdelta2 were overrepresented on T cells in milk as compared with blood. This selective compartmentalization seems to reflect the homing of certain cells to the mammary gland.

Increase of circulating CD8+CD57+ lymphocytes after measles infection but not after measles vaccination.

Natural measles virus infection is recognised to induce immunosuppression, contributing to an increased susceptibility to other infections. A cell population that could be involved in this process is the CD8CD57 double-positive lymphocyte subset (CD8+CD57+), known to be significantly expanded in some viral infections, e.g. human immunodeficiency virus (HIV) infection. We therefore studied the level of CD8+CD57+ lymphocytes during measles infection and measles vaccination. Twenty-two measles patients were examined 5-57 days after the onset of fever and several months later. Healthy, age-matched controls were examined twice. Eleven children receiving measles-mumps-rubella (MMR) vaccination were examined before, 9-19 days and 5-9 months afterwards. Blood samples were analysed for the proportion of peripheral blood mononuclear cells carrying both CD8 and CD57, and for other cell surface markers (CD4, CD14, CD3, CD16(CD56) or CD20). Elevated proportions of CD8CD57 double-positive cells were found in the peripheral blood of children with natural measles early after infection (p < 0.05), whereas the proportion of other cell surface markers remained stable. No corresponding change in CD8+CD57+ lymphocytes was noted in MMR-vaccinated children or in healthy controls. Since CD8+CD57+ lymphocytes could be related to the immunosuppression seen in some viral infections, our finding of elevated CD8CD57 double-positive lymphocytes during acute measles infection would suggest that this population of lymphocytes is involved in measles-induced immunosuppression. The absence of an increase of CD8CD57 in children vaccinated with the conventional live attenuated measles vaccine, in contrast to children with natural measles infection, would thus indicate that the vaccine does not induce immunosuppression as measured in our in vitro system.

Use of a historical register in social epidemiology: child mortality in Stockholm at the turn of the 19th century.

This study describes the age- and cause-specific levels and social determinants of high child mortality in Stockholm around the turn of the century. The study is based on computerized individual level sociodemographic information and the death certificates of children aged 0-15 years residing in Maria parish in Stockholm during the years 1885, 1891 and 1910 (n = 36,718) from a historical register (the Roteman archives). The usefulness of such data for further studies in social epidemiology is discussed. Age-specific rates and major causes of death compared well with other studies. Low social class and being born out of wedlock increased the overall risk of death in early childhood. Data appear valid and may be useful in social epidemiology. Further analyses of data from the Roteman archives may contribute to the understanding of causes behind high levels of cause- specific child mortality and trends in mortality in relation to societal change.

Whole-blood microassay for immunodetection of antigen specific cell mediated immunity using bromodeoxyuridine incorporation.

The study evaluates a novel version of the bromodeoxyuridine (BrdU) incorporation assay for in vitro proliferative responses, which works with finger-prick blood specimens. It was developed primarily for field-work involving children in Africa and elsewhere. Heparinized blood specimens from healthy volunteers were diluted 1:15 and cultured with purified protein derivative, tetanus toxoid, concanavalin A or medium alone for four-seven days and pulsed during the last 24 hours with bromodeoxyuridine. Thereafter, white and red cells were separated by Ficoll-Pacque centrifugation. The white cells were made to adhere to Multitest slides pre-treated with poly-L-lysin. After fixation with paraformaldehyde, the cells were incubated with mouse monoclonal antibodies to a surface marker for activated T cells (CD25, interleukin-2 receptor) and the reaction visualized with anti-mouse alkaline phosphatase conjugated antibodies and a Fast Red substrate. After treatment with cold acetone, the cells were covered with formamide and heated to 70 degrees C, without loss of surface staining. The incorporation of bromodeoxyuridine was visualized in the UV-microscope with mouse anti-bromodeoxyuridine monoclonal antibodies and a rabbit anti-mouse fluorescein conjugate. Both the surface staining and the nuclear fluorescence can be seen in UV-light and the cells be classified as single- or double-positive or negative. Parallel experiments on the same blood-sample from seven donors allowed for at least 42 paired comparisons between the proportion of BrdU positive cells and thymidine incorporation stimulation indices. The latter assay was carried out both in the conventional version and in a whole-blood micro-version. The rank order correlations were 0.84 and 0.91 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Rotavirus serology and breast-feeding in young children in rural Guinea-Bissau.

One hundred and forty-four children aged 9-20 months living in 14 villages in a rural area of Guinea-Bissau were examined for circulating rotavirus antibodies twice in a 15-month period. An immunofluorescence technique was used. About 3/4 of the children seroconverted, independent of age on entering the study. The age-specific proportion of seropositivity increased from 4/40 (10%) at 9-11 months to 26/29 (90%) at 33-35 months of age. All the initially seropositive children retained detectable antibodies to rotavirus. The relative risk of seroconversion was 1.4 times (95% confidence interval 1.0-2.0) more common among children living in villages by the mainroad as compared to those living off the road. Contact rate is probably dependent on population density and mobility but not on age. Breast-feeding, decreasing sharply through the age interval covered by the follow-up (9-35 months), had no apparent influence on seroconversion at the ages concerned.

PIP: The object of this study was to examine the effects of breast feeding, age, and residence location on rotavirus seropositivity among children in Guinea-Bissau. Blood samples were taken from 144 breast fed children aged 9-20 months. Blood samples were taken again 15 months later. The cumulative incidence of seroconversion was 76% or about 3/4 of each of the initial age groups (9-11 months, 12-14 months, 15-17 months, and 18-20 months). At the beginning of the study seropositivity increased with age. After 15 months it showed a further gradual increase with age. The children in the 9-11 month group were mostly still breast fed 15 months later, while those in the 18-20 month group were mostly weaned 15 months later. But the cumulative incidence of seropositivity remained 3/4. On the other hand, children living along the main road had a 40% higher risk of seroconverting as compared to children living off the road. Since age and breast feeding do not appear to be associated directly with seroconversion, it may be that travel patterns in the dry season contribute to the seasonality of rotavirus infection.

Follow-up of the antibody response to measles vaccine in a rural area of Guinea-Bissau.

One hundred and fourty-four children who either were already immune or had been successfully immunized against measles were reexamined after 16 months. All still had circulating Elisa antibodies at a clearly detectable level. Titres were higher in the group of children stated to have had measles prior to the immunization. None of the children had measles after immunization. Boostering by the wild virus may have occurred, whereas no evidence of a booster effect from the vaccine was found. About one third of the children were underweight. Plasmodium falciparum parasitaemia rate, and also its seasonality, varied with the location of the child's homestead. Even children exposed to mesoendemic P. falciparum malaria and moderate malnutrition can be successfully immunized with a conventional live attenuated measles vaccine from 8 months of age, which probably results in a lasting protection.

Augmented antibody response to live attenuated measles vaccine in children with Plasmodium falciparum parasitaemia.

The impact of malarial infection on the humoral immunological response to measles virus antigen was studied in 184 children aged 8-19 months in Guinea-Bissau. Pre- and post-immunization measles serology was performed using dried blood on absorbent paper and the ELISA technique. Blood smears obtained at the time of vaccination and 2 and 4 weeks afterwards were examined for malaria parasites. Pre-vaccination antibodies to measles were found in 44 out of 184 children (24%). Plasmodium falciparum was identified in 62 of the 132 initially non-immune children who completed the study. The rate of seroconversion was 127 out of 132 (96%). Post-immunization measles antibody titres were significantly higher in the vaccinees with P. falciparum than in those without malaria parasites in the blood.

Immunosuppression after measles vaccination.

The influence of conventional live attenuated measles vaccine on cellular immune responsiveness was investigated in Sweden and Guinea-Bissau. Sixteen children in a residential area in Bissau and 16 living in southern Stockholm were examined before and 8-10 days after vaccination. Lymphoproliferation was measured to concanavalin A (con-A), PPD and tetanus toxoid (TT) using a whole-blood 3H-thymidine incorporation assay. Stimulation indices were significantly lower after vaccination than before, in the case of con-A (p = 0.03) and TT (p = 0.01) in the Guinean children and in the case of PPD (p = 0.009) and TT (p = 0.03) in the Swedish children. Stimulation of lymphocytes from measles-immune children with measles antigens resulted in weak lymphoproliferative responses. These observations may be relevant to the increased mortality found in children immunized with high-titre measles vaccines, as compared to controls, in recent studies. The study confirms the applicability and usefulness under field conditions of the whole blood version of the thymidine incorporation assay.