The Relationship between Metabolic Acidosis and Nutritional Parameters in Patients on Hemodialysis.

The progressive loss of kidney function is accompanied by metabolic acidosis. The relationship between metabolic acidosis, nutritional status, and oral bicarbonate supplementation has not been assessed in the Indian chronic kidney disease (CKD) population who are on maintenance hemodialysis (MHD). This is a single-center prospective study conducted in the Western part of India. Thirty-five patients, who were receiving MHD were assessed for metabolic acidosis along with various nutritional parameters at the baseline and at the follow-up after 3 months, postcorrection of acidosis with oral sodium bicarbonate supplements. The relationship between the correction of metabolic acidosis with oral bicarbonate supplements and changes in dietary and various nutritional parameters were evaluated. Metabolic acidosis at the baseline evaluation was found in 62.86% cases of the cohort with a mean serum bicarbonate value of 20.18 ± 4.93 mmol/L. The correction of acidosis with increment in the mean dosage of oral sodium bicarbonate supplements from 0.69 ± 0.410 mmol/kg/day at baseline to 1.04 ± 0.612 mmol/kg/day, significantly reduced the prevalence of metabolic acidosis to 23.33% cases at the follow-up. Improvement in serum bicarbonate level showed significant dietary, anthropometric, and nutritional improvements in these patients. Hence, we conclude that correction of metabolic acidosis with optimal oral bicarbonate supplementation plays a pivotal role in the treatment of malnourished CKD patients on MHD.

A comparison of ex vivo cytokine production in venous and capillary blood.

We performed a randomized study of the immunological effects of an early measles vaccine given at 4.5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained. We analysed baseline samples from the first 50 children enrolled in the study to investigate the potential differences in ex vivo cytokine production between venous blood and capillary blood. We also obtained paired venous and capillary blood samples from 11 adult volunteers. Whole blood was stimulated with lipopolysaccharide (LPS) [a Toll-like receptor (TLR)-4 ligand], (S)-(2, 3-bis (palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, trihydrochloride (PAM3Cys) (a TLR-2 ligand), phytohaemagglutinin (PHA) or purified protein derivative (PPD). Cytokine concentrations in the supernatants were assessed by a multiplexed assay and were compared between venous and capillary samples in both infants and adults. The production of both the pro- and the anti-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10, was higher in cultures of capillary blood compared with venous blood. This was found in non-stimulated control samples as well as in blood stimulated with PAM3Cys and PPD. Adults produced more IL-5 in venous blood than in capillary blood upon PHA stimulation. We found no other difference in the levels of IL-5 or IFN-gamma between venous and capillary blood. In capillary blood we found sex differences in response to PHA but this was not the case in venous blood. We found significant differences in the production of cytokines between venous and capillary blood. Such differences should be taken into account when setting up immuno-epidemiological studies.

Reduced case fatality among hospitalized children during a war in Guinea-Bissau: a lesson in equity.

BACKGROUND: During a recent armed conflict in Guinea-Bissau, we observed a marked decline in the case fatality among hospitalized children at the only paediatric department in the country. AIM: To analyse the causes behind the observed fall in case fatality. MATERIAL: All children hospitalized at the only paediatric department in the capital of Guinea-Bissau. The war cohort comprised all children hospitalized during the war, which lasted from June 1998 to May 1999, and the peace cohort comprised all children hospitalized in the year preceding the war. As part of a longitudinal community study, we also registered all children being hospitalized from the Bandim Health Project's study area, including routinely collected information on socio-economic background factors. METHODS: The war cohort was compared with the peace cohort in terms of determinants for hospital case fatality. Through information in the community register, we examined post-hospital mortality in the 2 wk after discharge as well as socio-economic differences in recruitment during the war. Hospital case fatality was estimated by odds ratios and compared by multiple logistic regression. Community mortality risk was estimated by deaths per person years. RESULTS: The case fatality among children aged 0-14 y fell during the war (age-adjusted OR = 0.58; 95% CI: 0.50-0.68). There was a uniform reduction in case fatality among children hospitalized less than 7 d, while we observed no decline among children hospitalized longer. There were more children per bed during the war and mean hospitalization time was shorter, and post-discharge mortality also fell (mortality ratio (MR) = 0.57; 95% CI: 0.40-0.83). Adjustment for socio-economic confounders in recruitment during the war period made no difference to the estimated decline in case fatality. The decline in case fatality at the hospital was not explained by a general decline in mortality. Compared with the preceding year, the mortality ratio was 1.34 (1.20-1.51) in the Bandim Health Project's study area during the war. Adjusted for age, the decline in case fatality at the hospital was most marked for disadvantaged groups. For example, the general reduction in case fatality was 42% (95% CI: 11-63); however, children of mothers without any schooling experienced a reduction of 73% (95% CI: 27-90%), whereas the reduction was only 33% (95% CI: 14-61%) for children of mothers with school education. CONCLUSION: The decline in case fatality could be explained neither by a general decline in childhood mortality nor by changes in recruitment or discharge policy. The decline was therefore most likely due to improved treatment as a result of better availability of drugs funded by humanitarian aid and the presence of dedicated staff, which was offered relief food as compensation. Interventions improving case management may have a proportionately larger effect for poor families.

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

Measles antibody responses after early two dose trials in Guinea-Bissau with Edmonston-Zagreb and Schwarz standard-titre measles vaccine: better antibody increase from booster dose of the Edmonston-Zagreb vaccine.

In Guinea-Bissau, children were randomised at 6 months of age to receive either two doses of standard-titre measles vaccine at 6 and 9 months of age or an inactivated polio vaccine at 6 months and standard-titre measles vaccine at 9 months of age. During the first 5 months, children received Edmonston-Zagreb (EZ) vaccine and during the following 11 months, the Schwarz (SW) vaccine. Five percent of the mothers, 74% of children at 6 months of age, and 92% of unvaccinated children at 9 months of age had unprotective levels (<125 mIU/ml) of measles antibodies. Among children receiving EZ vaccine, 1% were unprotected at 18 months of age after either two (3/240) or one (3/211) doses of vaccine, the geometric mean measles antibody titre (GMT) being approximately 1550 mIU/ml in both groups. Among those receiving SW vaccine 9% (34/365) and 3% (9/310) were unprotected at 18 months of age in the two-dose and the one-dose groups (RR = 3.21 (95% confidence interval (CI) 1.56-6.58)), respectively. The GMT was higher after one dose of SW vaccine at 9 months of age (2491 mIU/ml) than after two doses of SW vaccine (1125 mIU) (P < 0.001). In the EZ vaccine group, there was no significant difference in antibody level for children vaccinated in the presence of high or low levels of maternal antibodies, whereas there was a marked difference in the SW group. The second EZ vaccine induced a significant antibody increase between 9 months of age (1191 mIU) and 18 months of age (1602 mIU, P=0.011), whereas antibody levels tended to decline from 9 months (1243 mIU) to 18 months of age (998 mIU, P = 0.124) after the second dose of SW vaccine. Conclusively, after two doses of EZ measles vaccine more children were protected at 18 months of age than after two doses of SW. One dose of SW provided the highest antibody response, but a higher proportion of unprotected than one or two doses of EZ. The EZ vaccine was less sensitive to maternal antibodies, and able to increase the antibody response by revaccination, while the second SW vaccine resulted in an unchanged or lower antibody response.

No strong long-term effect of vitamin A supplementation in infancy on CD4 and CD8 T-cell subsets. A community study from Guinea-Bissau, West Africa.

The World Health Organization recommends that 100,000 IU of vitamin A be given to infants between 6 and 12 months of age at the same time as measles vaccination in order to prevent vitamin A deficiency. In the present study, our aim was to assess the effect of vitamin A supplementation on T-cell subsets in a randomized factorial design, seeking a possible modifying effect of measles vaccination. Three hundred children were allocated either to two doses of measles vaccine at 6 and 9 months of age or to poliomyelitis vaccine at age 6 months and measles vaccine at age 9 months. Within each group, infants were to receive two doses of vitamin A or two doses of placebo at 6 and 9 months of age. We found no significant effect of vitamin A supplementation on CD4 and CD8 T-cell subsets at 3 and 9 months after supplementation. We found no effect of measles vaccine and no interaction between vitamin A supplementation and measles vaccine. Based on these observations, vitamin A supplementation does not seem to have a strong long-term effect on CD4 and CD8 T-cell subsets in infants without clinical vitamin A deficiency.

Early two-dose measles vaccination schedule in Guinea-Bissau: good protection and coverage in infancy.

BACKGROUND: Previous studies from Africa have suggested that there is little benefit to be gained from early two-dose measles vaccination schedules. Two-dose schedules have been associated with no improvement in coverage due to immunization of the same individuals on both occasions, low return rate, high refusal rate, low vaccine efficacy, and fear of blunting of the antibody response. Because of the poor results achieved previously with two-dose measles vaccination schedules, we studied patterns of participation, reasons for non-participation, vaccination coverage and relative efficacy of a one-dose versus a two-dose schedule in connection with the implementation of an early two-dose trial in Guinea-Bissau. METHODS: Children born from September 1994 to January 1996 were randomized into two groups receiving either two doses of measles vaccine at 6 and 9 months or one dose of inactivated polio vaccine (IPV) at 6 months and measles vaccine at 9 months. RESULTS: At 6 months of age 86% (1869/2181) of the children participated, and at 9 months of age participation was 87% (1775/2035). The return rate for obtaining a second dose of vaccine was 93% (1647/1773). The main reason for not participating was travelling (78%). Around 50% of those who did not take part in one vaccination took part in the other. When only children participating the first time they were called for a measles vaccination were included, the measles vaccination coverage in the one-dose group was 59% versus 80% in the two-dose group, i.e. a 50% reduction in the risk of not being vaccinated (relative risk [RR] 0.50; confidence interval [CI]: 0.43-0.57). Few measles cases have occurred in the study area since the implementation of the trial making precise estimation of the relative efficacy of the two vaccine strategies difficult, but all seven clinically diagnosed measles cases occurred in the one-dose group making the relative efficacy for the two-dose group compared with the one-dose group 100% (95% CI: 35%-100%; two-tailed P = 0.016). When including maternal reports, the relative efficacy was 90% (95% exact confidence interval; two-tailed P = 25%-97%, P = 0.022). CONCLUSION: In this study of a two-dose measles immunization schedule at 6 and 9 months of age there was no sign of low participation or poor return rates. The risk of not being vaccinated was lower in the two-dose group than in the one-dose group, and the relative efficacy of a two-dose versus a one-dose schedule was high. Although our results were obtained within a trial where dedicated personnel informed every participant personally about the study, we believe our results indicate that with thorough information about the population it may be possible to achieve a higher coverage with a two-dose measles vaccination schedule than a one-dose schedule. A two-dose schedule may be a feasible way to resolve the problems of low coverage and severe measles infection among infants.

PIP: Early 2-dose measles vaccination schedules in Africa have been associated with no improvement in coverage due to immunization of the same individuals on both occasions, low return rate, high refusal rate, low vaccine efficacy, and fear of blunting the antibody response. Findings are presented from the study of patterns of vaccination participation, reasons for nonparticipation, vaccination coverage, and the relative efficacy of a 1-dose versus 2-dose schedule in connection with the implementation of an early 2-dose trial in Guinea-Bissau. Children born from September 1994 to January 1996 were randomized into 2 groups receiving either 2 doses of measles vaccine at 6 and 9 months or 1 dose of inactivated polio vaccine (IPV) at age 6 months and measles vaccine at 9 months. 93% of children returned to receive a second dose of vaccine, with the main reason for nonparticipation being the need to travel. About half of the children who did not participate in 1 vaccination took part in the other. There was no sign of low participation or poor return rates in this study of a 2-dose measles immunization schedule at ages 6 and 9 months. The risk of not being vaccinated was lower in the 2-dose group than in the 1-dose group, and the relative efficacy of a 2-dose versus 1-dose schedule was high. These results indicate that with thorough information about the population it may be possible to achieve higher coverage with a 2-dose measles vaccination schedule than with a 1-dose schedule. A 2-dose schedule may be a feasible way of resolving the problems of low coverage and severe measles infection among infants.

Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa.

BACKGROUND: WHO has recommended vitamin A supplementation for children aged 6 months or older in developing countries at the same time as immunisation. One study has reported significantly lower seroconversion ratios among children who have received vitamin A supplements with measles vaccine at age 6 months. The aim of our study was to assess the effect of vitamin A supplementation on antibody response to measles vaccination at age 9 months, which is the more common age for immunisation in developing countries. METHODS: In an urban community in Guinea-Bissau, we did a randomised, double-blind, placebo-controlled study of the effect of simultaneous vaccination and vitamin A supplementation in 462 children who received either a two-dose schedule of measles vaccine at the ages of 6 months and 9 months (150 infants) or one dose of measles vaccine at age 9 months (312 infants). Children were followed up to the age of 18 months and a blood sample was then collected to assess the antibody response. FINDINGS: 397 (86%) of the children took part in the follow-up (52 [11%] had moved and 13 [3%] had died). Among children who received a two-dose vaccine schedule, seroconversion was 98%. There was no difference in seroconversion or geometric mean titre (GMT) for children receiving vitamin A compared with children receiving no supplement. Among children receiving only one dose of measles vaccine at age 9 months, seroconversion was 95%. The GMT was significantly higher in children receiving vitamin A than in those receiving no supplement (3704 vs 2439 mIU; GMT ratio 1.52 [1.22-1.88]). The effect on plasma antibody concentration in the blood was stronger for boys (3902 vs 1916 mIU; GMT ratio 2.04 [1.53-2.72]) than for girls (3502 vs 3017 mIU; GMT ratio 1.16 [0.85-1.58]) who had received vitamin A with measles vaccine. In a multivariate analysis of variance adjusted for sex, vitamin A supplementation was associated with higher antibody titres (p < 0.001). There was a significant interaction between vitamin A supplementation and sex (p = 0.02). INTERPRETATION: There is no indication that simultaneous administration of measles vaccine and vitamin A supplements has a negative effect on measles immunity. Among the children who had received two doses of measles vaccine at the ages of 6 months and 9 months, supplements of vitamin A had no significant effect. Among children only receiving one dose of measles vaccine at age 9 months, 100,000 IU vitamin A increased antibody concentrations, especially for boys.

Interval to delivery in high-risk patients: do tocolytic agents really work?

Some question whether tocolytic drugs reduce uterine activity and prolong gestation. The interval from discontinuance of tocolytics until spontaneous labor and delivery in patients (n = 69) with documented preterm labor (PTL) versus subjects receiving prophylactic tocolytic therapy (n = 41) was studied. Women with documented PTL delivered sooner after cessation of tocolytics (6.1 +/- 6.9 days) than control (C) patients (14.7 +/- 10.8 days, P less than 0.001). Also, 28 of the 69 (41%) patients in the PTL group delivered within 24 h of discontinuation of tocolysis compared to 4 (10%) in the C group (P less than 0.0004). We conclude that tocolytic therapy for documented preterm labor suppresses uterine activity and when these agents are discontinued, contractions return and labor ensues.