Influence of nutrition on postvaccinial tuberculin sensitivity.

Response to BCG vaccination was studied in 261 apparently normal preschool children in a community. They were classified into different nutritional groups based on deficit in weight for age. In addition, nine children who had kwashiorkor and were admitted to the hospital were investigated. They were given 0.1 ml of BCG vaccine, and 6 months later, tuberculin sensitivity was assessed using 5 U of PPD. Blood samples were collected from 84 subjects and leukocyte migration inhibition was determined using the same antigen. After BCG vaccination, over 80% of children in the community showed positive tuberculin test, irrespective of the extent of growth retardation. There were no significant differences in the size of induration or the percentage of reactors between the various groups, indicating that the immune response to BCG vaccination is not affected by milder grades of malnutrition. However, the skin test was negative in most of the children who had had kwashiorkor. Leukocyte migration inhibition was similar in all the groups of children including those with kwashiorkor indicating that sensitisation of lymphocytes was not influenced by the nutritional status. In children with kwashiorkor, the leukocyte migration inhibition test was positive though the skin test was negative, suggesting that the former may be a better measure of assessing the response to BCG vaccination.

Rose Bengal staining for detection of conjunctival xerosis in nutrition surveys.

A hospital cum community based study indicated that rose Bengal staining of the eye could not only confirm clinically diagnosed cases of conjunctival xerosis but also detect those missed by clinical examination. However, some cases thus detected did not respond to a massive oral dose of vitamin A.

Relationship between measles, malnutrition, and blindness: a prospective study in Indian children.

A prospective study was conducted in slum children to determine the incidence of post-measles corneal disease and to clarify its relationship with nutritional status. A total of 318 cases of measles were identified over a period of 15 mo; maximum incidence was observed for children between 1-2 yr. Most of the children showed weight loss and serum proteins decrease during the acute stage of measles. Corneal lesions were observed in 3% of the children, and the lesions responded well to treatment. Serum vitamin A and RBP levels were significantly depressed during the acute stage of measles but were restored to normal 8 wk after recovery. There were no significant differences in the serum levels for those with and without eye lesions, which suggests that these lesions may not be mediated simply through the effect of infection on serum concentration of vitamin A.

Peripheral blood monocyte function in malnourished subjects with pulmonary tuberculosis.

The effect of associated malnutrition on the functional status of peripheral blood monocytes activated in vitro was tested in patients suffering from pulmonary tuberculosis, contacts and healthy controls. The capacity of the in vitro activated monocytes (MO) to generate hydrogen peroxide (H2O2), superoxide (O-2) and interleukin-1 (IL1) was tested. The results indicated that the patients and contacts were significantly malnourished compared to the controls. The MO functions, however, were comparable among the three groups indicating lack of in vivo activation of the MO in patients harbouring tubercular infection/disease. With the evidence available from the literature on the effects of malnutrition on cellular immune functions, it was speculated that the observed MO dysfunction could be due to lack of appropriate lymphokine elaboration due to associated malnutrition. The observed immunological defect might increase the risk of overt infection among the malnourished contacts.

Role of zinc supplementation in the rehabilitation of severely malnourished children.

A double-blind study was conducted to assess the role of zinc supplementation in the rehabilitation of severely malnourished children. Thirty-three children with severe protein-energy malnutrition received either 40 mg of zinc as zinc sulphate or a placebo during their rehabilitation in addition to the diet containing about 700 kJ and 3-4 g protein per kg body weight/day. Their clinical and biochemical responses were examined. Clinical response and serum albumin synthesis were found to be similar in both the groups. The leukocyte (micrograms/10(10) cells) and plasma zinc levels (micrograms/dl) showed a significant (P < 0.001 and P < 0.01) increase from 46.9 +/- 5.490 to 107.2 +/- 13.224 and 80.4 +/- 9.972 to 107.5 +/- 11.822, respectively, after zinc supplementation. The placebo group also showed a significant (P < 0.025) increase in leukocyte zinc from 45.7 +/- 4.409 to 70.9 +/- 8.414. However, the plasma zinc in the placebo group fell from 83.6 +/- 10.363 to 68.2 +/- 7.031. Plasma copper showed a significant improvement in both zinc supplemented (P < 0.01) and placebo (P < 0.025) groups. The results indicate that zinc supplementation along with the diet would result in rapid restoration of zinc status, though there is no effect on the weight gain or other responses.

Serum transferrin receptor in children with respiratory infections.

OBJECTIVE: To study the effect of infection on iron status in children suffering from acute, mild or severe respiratory infections and to determine the nature of anemia in infection using serum transferrin receptor (sTfR) levels. DESIGN: Forty-three children aged between 3 and 5 y with no evidence of infection and receiving iron supplements in the preceding 100 days served as controls. Twenty-one children with mild upper respiratory infection and 94 children hospitalized for acute pneumonia constituted the experimental group. Hemoglobin (Hb), sTfR and serum ferritin were estimated in all the children at the time of diagnosis and again on the 15th and 30th days after the infection in those who were available for follow-up. RESULTS: Mean (95% CI) sTfR was 6.08 (5.1-7.1) mg/l in healthy non-anemic children. Upper respiratory infection had no impact on Hb or sTfR but it significantly elevated serum ferritin levels. Eighty-three percent of the children with pneumonia had Hb less than 110 g/l at the time of diagnosis and had elevated mean sTfR, 18.0 (15.7-20.3) mg/l. There was a decline in mean sTfR by the 15th day of infection to 14.3 (11.3-17.4) mg/l with further rise to 22.9 (13.0-31.9) mg/l by 30 days. Serum ferritin was significantly elevated at the time of diagnosis (85.9; 71.1-100.8 micro g/l) as well as at 15 days (89.1; 68-110.1 micro g/l) with a decline by 30 days. CONCLUSIONS: Severe lower respiratory infection exaggerates iron-deficient erythropoiesis by blocking release of iron from the storage pools. sTfR may not be a sensitive and specific tool of assessing true iron status of children exposed to severe infections.

Measles & malnutrition.

Measles is an important acute childhood viral infection having severe consequences on the nutritional status. The adverse nutritional effects of measles are experienced by both the well-nourished and the malnourished children. However, the severe nutritional deficiencies like kwashiorkor/marasmus are precipitated only in children who are already malnourished. As high as 3-4 per cent of children with measles suffered from these clinical nutritional syndromes in their post-measles period. Though malnutrition is widespread among Asian children also, measles appears to run a milder course with low mortality rates in developing Asian countries, as compared to African children. The associated secondary infections which apparently complicate the primary illness in malnourished children might be responsible for higher mortality and could be due to socioeconomic and environmental causes that are associated with poverty and malnutrition rather than due to malnutrition or measles per se. Measles related blindness is of multifactorial aetiology. While acute measles triggers corneal ulceration through viral proliferation in the cornea, nutritional keratomalacia is often the cause of blindness in the post-measles period. Measles vaccination is the major preventive measure. However, timely use of local antibiotic therapy to the eyes and administration of vitamin A supplements offer protection to the child who already has measles. Response of malnourished children to live attenuated measles vaccine has been found to be safe and effective. Neither malnutrition nor tuberculosis which are widespread among malnourished children of developing countries appear to be contraindications for measles vaccination. Thus, the beneficial effects of the measles vaccination should be fully exploited by adequate supply of potent vaccine and coverage of all susceptible children.

Zinc status of Indian children.

Zinc is a trace metal essential for human health and its deficiency is found to cause severe growth retardation in children. Information on the zinc status of Indian children is meagre perhaps due to lack of a reliable parameter. However, in view of the role of zinc in promoting growth, it has become common practice to prescribe zinc supplements to young children and newborns, particularly preterm infants. It is now clearly established that zinc confers no additional benefits to an individual with adequate zinc status while it can potentially lead to harmful effects by disturbing the milieu of other trace metals in the body. Estimation of thymulin levels in circulation is found to be a sensitive indicator of zinc status and using this parameter we found that apparently normal children have adequate zinc status. Children suffering from severe protein energy malnutrition however had very low levels of the hormone besides low leukocyte and plasma zinc levels indicating zinc deficiency. Such children showed improvement in their zinc status when zinc supplements were provided along with rehabilitation diets. Pregnant women and term newborns showed no evidence of zinc deficiency. Preterm infants had higher leukocyte zinc levels during early infancy and the breast milk of their mothers also had higher zinc content which could cater to the higher requirements of the rapidly growing preterm infant. All breast-fed infants showed decline in the zinc status gradually over the initial 4 months of life and regained adequate zinc status after appropriate weaning. These studies thus do not support the view of routine zinc supplements to pregnant women or children. However, Infants solely fed formula milk from birth had significantly impaired zinc status till the time of weaning. The functional significance of severe zinc inadequacy in such infants needs to be established.

Specific immune responses in typhoid fever & after TAB vaccination.

The specific immune responses to Salmonella typhi were investigated in 131 patients suffering from typhoid fever and 34 healthy individuals after TAB vaccination. A proportion of individuals failed to develop either specific humoral or cell mediated immune responses. About 5 per cent of the patients with natural infection and nearly 9 per cent of the vaccine recipients failed to develop both the responses. Frequent reinfection and carrier state, and lack of absolute protection following TAB vaccination could be due to the inability of a proportion of naturally infected and TAB vaccinated individuals to mount sufficient specific immune responses, due to the same mechanism.

Association of tumour necrosis factor alpha & malnutrition with outcome in children with acute bacterial meningitis.

BACKGROUND & OBJECTIVES: Tumour necrosis factor alpha (TNF alpha) is implicated in the pathogenesis of acute bacterial meningitis (ABM). However, we do not know if the nutritional status influences the concentration of TNF alpha in the CSF in children with ABM. The present study evaluates the association between malnutrition and TNF alpha detectability in CSF and the outcome from ABM in children. METHODS: A total of 120 children aged 1-5 yr diagnosed as ABM, based on the standard criteria of CSF changes were recruited for the study. A CSF sample was collected at the time of admission. TNF alpha was measured by ELISA and CSF culture was done by standard technique. Nutritional status was assessed by anthropometry. Outcome was measured by clinical examination. RESULTS: Of the 120 children, 20 died, 36 developed complications and 64 children recovered without sequelae. TNF alpha was detectable in 94 (78.3%) CSF samples, with a range of 32 to 1714 pg/ml. TNF alpha detectability was not associated with either nutritional status or with death and sequelae. However, death and sequelae were significantly (P = 0.01) associated with malnutrition. INTERPRETATION & CONCLUSION: CSF TNF alpha was not associated with nutritional status. However, malnutrition was associated with adverse outcome due to ABM in children.

Post-vaccination scenario of measles: a retrospective analysis.

BACKGROUND: Routine vaccination against measles was introduced in India during 1985-86 through the Universal Immunization Programme. Its effect on the current prevalence of measles is not known. METHODS: Information on the total number of patients admitted and deaths due to measles from January 1982 to December 1997 were obtained from the records of the Institute of Tropical Medicine, Hyderabad, the only infectious diseases hospital in the city. Details on age, sex, number of complications, duration of hospital stay, vaccination status and information on vitamin A administration in the hospital were collected from the case records. RESULTS: A total of 20,926 cases of measles were admitted from 1982 to 1997. There was a 69% reduction in hospital admissions from the pre-vaccination to the post-vaccination period, and deaths due to measles decreased by 90%. Over the years, a rise in the age of children admitted with measles was observed. Boys were admitted more frequently to the hospital (p < 0.001) than girls. All the children showed one or more complications. From 1992 onwards, vitamin A was administered to 45.4% of the children admitted. CONCLUSION: A significant reduction was observed in the number of cases admitted to the hospital as well as deaths due to measles. Apart from the effect of the vaccination programme, this could also be due to increased awareness and availability of better health care facilities in the hospital and peripheral health clinics. Administration of vitamin A to children with measles as recommended by the World Health Organization needs to be implemented. A significant increase in the number of older children (> 5 years) with no significant reduction in the infants affected by measles indicates inadequate vaccine coverage and accumulation of susceptible older children.

Red palm oil supplementation: a feasible diet-based approach to improve the vitamin A status of pregnant women and their infants.

This double-blinded, randomized, controlled study was designed to study the effect of dietary supplementation with red palm oil during pregnancy on maternal and neonatal vitamin A status. A total of 170 women were recruited at 16 to 24 weeks of gestation and randomly assigned to an experimental group that received red palm oil to supply approximately one recommended dietary amount (RDA) (2,400 micrograms) of beta-carotene or to a control group that received an equivalent volume of groundnut oil. The women received the oils for a period of 8 weeks, starting at 26 to 28 weeks of gestation and extending to 34 to 36 weeks of gestation. The mean postintervention (34 to 36 weeks) levels of serum retinol were 1.20 +/- 0.22 (SD) mumol/L (95% CI, 1.15-1.25) in women receiving red palm oil and 0.73 +/- 0.15 mumol/L (95% CI, 0.69-0.77) in their infants; these levels were significantly higher than those in women receiving groundnut oil (1.07 +/- 0.26 mumol/L; 95% CI, 1.01-1.13; p < .01) and their infants (0.62 +/- 0.17 mumol/L; 95% CI, 0.57-0.67; p < .001). A significantly lower proportion of women in the red palm oil group than in the control group had vitamin A deficiency (serum retinol levels < 0.7 mumol/L) after intervention (1.5% vs. 9.7%). The proportion of women having anemia was significantly lower (p < .01) in the red palm oil-supplemented group (80.6%) than in the control group (96.7%). The mean birthweight and gestational age of the infants did not differ significantly between the two groups. An increased risk of low birth-weight (p = .003) and preterm delivery (p = .000) was observed with decreasing serum retinol levels in the third trimester of pregnancy. These results show that red palm oil supplementation significantly improved maternal and neonatal vitamin A status and reduced the prevalence of maternal anemia. Maternal vitamin A status in the later part of pregnancy is significantly associated with fetal growth and maturation. Hence red palm oil, a rich source of bioavailable vitamin A, could be used as a diet-based approach for improving vitamin A status in pregnancy.

Safety and impact of vitamin A supplementation delivered with oral polio vaccine as part of the immunization campaign in Orissa, India.

A study was carried out in Orissa, India, to evaluate the impact on vitamin A status of vitamin A supplementation integrated with an immunization campaign. Data were collected from a representative sample of 1,811 children, aged 12 to 48 months, at baseline and then at 4 and 16 weeks following implementation of vitamin A supplementation. The primary outcome indicator was serum retinol. The coverage of vitamin A supplementation was 97%. There was a significant decline in the prevalence of Bitot's spots from 2.9% to 1.9% at 4 weeks, but the prevalence increased to 3.6% by 16 weeks. Serum retinol concentrations increased between baseline and 4 weeks (from 0.62 +/- 0.32 to 0.73 +/- 0.23 mumol/L, p < .001) but then decreased to 0.50 +/- 0.19 mumol/l at 16 weeks, which was significantly lower than at baseline (p < .001). The greatest increase in serum retinol from baseline to 4-week follow-up was among children with lowest baseline serum retinol and children with Bitot's spots at baseline. This study demonstrates the short-term benefits of vitamin A supplementation to be significant, especially for those whose status is most compromised. At the same time, the benefit of vitamin A supplementation in this population was transient. The impact of the vitamin A could not be sustained for the full 16 weeks in the study population. This finding calls for exploration of other means to improve vitamin A status, perhaps by adjusting the vitamin A supplementation schedule with more aggressive measures to improve intake of foods rich in bioavailable vitamin A, such as small amounts of animal foods or fortified foods. The study demonstrates the feasibility of integrating vitamin A supplementation with immunization campaigns.

Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9-months-old Indian infants.

The mutual interactions of measles vaccine and vitamin A dose when administered simultaneously to 9 month old infants are explored in this study. One hundred healthy infants of 9 months of age received EZ strain of measles vaccine in the routine immunization clinic along with either 100,000 IU of vitamin A or a placebo orally. Blood samples were collected before and 4 weeks after intervention. They were coded and analysed for serum retinol and Hemagglutination Inhibition (HI) antibodies to measles. Ninety five per cent of the infants were seronegative to measles prior to vaccination with a seroconversion rate of 63% in the control group and a significantly higher percent of 83.7% in the experimental group (P < 0.01). Seroconversion was not related to initial serum retinol levels in either of the groups. 42% of infants had serum retinol levels less than 20 ug/dl before administration of the vaccine and both the groups showed improvement in vitamin A status following intervention, the increase being significant in the experimental group (from 22.4 +/- 1.32 to 26.0 +/- 1.07; P < 0.05). The results indicate that majority of the infants at 9 months of age were seronegative to measles. Seroconversion to measles vaccine in the routine immunization clinics was low. Simultaneous administration of vitamin A and measles vaccine had beneficial effects on vitamin A status as well as seroconversion rates to the vaccine in 9 months old infants.

Need for protection against rubella in India.

Reports from different parts of India highlight the existence of Rubella leading to fetal malformations and wastage. However, the need for routine immunization to control rubella has not been duly recognized. In the present study the prevalence of rubella was determined in different age groups of the population by estimating IgG antibodies to rubella virus using ELISA kit obtained from Diamedix. Two hundred and seventy four pairs of maternal blood samples were collected. Samples were also obtained from one hundred and thirty nine children aged 1-15 years and assayed for rubella antibodies. The sample was read as positive if the Elisa unit/ml was 15 EU/ml. The results showed that 94.9% of mothers and 94.1% of cord blood samples showed seropositivity. Children between 1 and 5 years showed the lowest seropositivity of 69.2% which gradually increased to reach near 95% levels by 15 years. These observations indicate the prevalence of rubella in children and thus suggest the need to protect susceptible women of reproductive age group.

Validation of hemoglobin estimation using Hemocue.

OBJECTIVE: This piece of work is an attempt to compare Hemocue and Cyanmethemoglobin methods for hemoglobin estimation. METHODS: In 100 apparently healthy children of 1-6 years of age, Hb was estimated using Hemocue and cyanmethemoglobin methods from finger prick blood sample. The results obtained by the two methods were compared using appropriate statistical methods. RESULTS: Mean +/- SD values for hemoglobin (g/dl) were 9.33 +/- 2.719 by Hemocue and 8.14 +/- 2.448 by cyanmethemoglobin method. When assessed by Hemocue method the proportion of children with anemia was 66% while it was 88% with cyanmethemoglobin method. The sensitivity of Hemocue method was 0.75 and specificity 1.0 considering cyanmethemoglobin method as gold standard. The corresponding values by cyanmethemoglobin method for a given Hemocue value fell within the Mean difference +/- 2 SD with correlation coefficient being r = 0.922. Despite the good association, the two methods agreed, the magnitude of difference being -1.19 g/dl (CI: -1.40 to -0.98) thus suggesting an overestimate of hemocue values ranging from 10 to 15%. A correction factor was arrived for converting Hb values obtained by Hemocue method to arrive at the expected value by the reference method, this factor being 0.389 + 0.831 Hb (Hemocue). CONCLUSION: As there are limitations expressed for both the methods in accurately estimating Hb, it is difficult to decide whether one is an overestimate or the other an underestimate. By virtue of the principle involved in estimating Hb, cyanmethemoglobin method may be taken as an indirect indicator of iron status. However, it is not clear whether such a principle is involved in estimating Hb by Hemocue. Therefore, these two methods need to be further validated against a sensitive and specific indicator for iron status like circulating transferrin receptor to decide which of the methods can be used to accurately determine the prevalence of iron deficiency anemia in the community.

Effect of administration of 200,000 IU of vitamin A to women within 24 hrs after delivery on response to PPV administered to the newborn.

OBJECTIVE: To explore the effect of maternal supplementation of vitamin A on the immune response to oral polio vaccine in breastfed infants. DESIGN: Randomized controlled trial. SETTING: Hospital based. METHODS: One hundred mothers having uncomplicated deliveries randomly received either 200,000 IU vitamin A orally (Experimental) or placebo (Control). All the newborns were given a dose of oral polio vaccine within 72 hours after birth and were breastfed. Type specific neutralizing antibodies to polio viruses in test sera diluted from 1:4 to 1:512 and serum retinol levels were determined from the cord blood and at the age of 6 weeks. Breast milk retinol levels were determined at 3, 10, 30, 45 and 90 days of lactation. RESULTS: Seroconversion to OPV and geometric means of antibody titers to the three types of polio viruses were comparable between the groups of infants belonging to the experimental and control mothers. Breast milk retinol levels were significantly higher in the experimental group upto 45-90 days of lactation. Majority of the infants at birth had serum retinol levels < 15 micrograms/dl which improved significantly by 6 weeks irrespective of the maternal supplementation status. CONCLUSIONS: Maternal vitamin A supplementation soon after delivery improves vitamin A intakes of breastfed infants during the first 3 months and has no interference with the seroconversion to a neonatal dose of OPV. OPV administered to newborn in turn has no adverse effect on the vitamin A status of the breastfed infants.

BCG vaccination in malnourished child population.

The efficacy of BCG vaccination is still a subject of controversy. In the present study the protective role of BCG vaccination, the influence of nutritional status and justification for revaccination in children were investigated. Of the 504 preschool children suffering from tuberculosis who were registered for the study, 345 children did not receive BCG vaccine while the others had it during early infancy. Vaccinated children showed a significantly greater tendency to localise the tubercular lesions while most of the unvaccinated children suffered from progressive forms of the infection. Vaccination had similar effects even when there was associated malnutrition. Age did not seem to influence the severity of the disease in unvaccinated children while older children (greater than 3 yrs) had a greater tendency to localise the lesion in the vaccinated group. These data do not support the proposal of administering a booster dose of BCG to children who were vaccinated during early infancy.

An outbreak of poliomyelitis in Andhra Pradesh (South India).

An outbreak of poliomyelitis that occurred in the year 1992 in Telangana region of Andhra Pradesh, South India was investigated to understand the reasons for persistence of poliomyelitis in the general population and for the outbreak in Andhra Pradesh in particular. The study comprised of a detailed investigation of epidemiological and clinical features, serology and vaccination status and a case control study to calculate vaccine efficacy by matched pair analysis. The outbreak occurred after a relative quiescence of 3 years. The age group of the patients ranged from 2 months to 5 years, 26.5% being infants and 70.2% being children between 1 and 5 years. The outbreak was mainly caused by Type 1 poliovirus. Vaccine efficacy was found to be 70%. Antibody response was not high in cases. Seventy six per cent of the children with poliomyelitis were unvaccinated. Ignorance of the mothers and family interference were the main causes for not vaccinating the children. The study indicates the need to increase the vaccination coverage and inclusion of children upto 5 years in the programme. Absence of vaccination is the major risk factor for the outbreak. The persistence of poliomyelitis in older children, low antibody response and suboptimal vaccine efficacy point out the problem of achieving control with OPV in tropical countries and suggest the need for alternate strategies. Better health education strategies need to be developed.

A direct ELISA technique to detect antibodies against polioviruses.

A direct ELISA test was developed to detect circulating antibodies specific to poliovirus types 1, 2 and 3. Specificity of the test was established by using known polio negative and positive sera. The assay was compared with the standard microneutralization test using sera from polio and non polio cases vaccinated and unvaccinated subjects and standard positive sera obtained from WHO/EPI (Geneva). The reproducibility of the results was tested using different batches of the antigen prepared from Sabin strain of poliovirus supplied by ERC Bombay and from Sabin strain of virus obtained from WHO/EPI. ELISA was found to be as sensitive as microneutralization test in detecting seronegatives and was found to be specific to polio by giving negative results with non polio cases. ELISA is thus a rapid and simple method that may be useful for mapping seroepidemiology of poliomyelitis and as a tool for effective surveillance of the disease by offering rapid diagnosis in acute cases.