Anja Poulsen

Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies

BACKGROUNDnFemales given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female-male mortality ratio.nnnMETHODSnIn three trials from West Africa, 2000 children were randomised to HTMV or control vaccine at 4-5 months of age; a second vaccination was given at age 9-10 months (standard measles vaccine). Children in high-titre groups were given IPV or DTP-IPV. Another 944 children received HTMV as routine vaccination in Senegal.nnnFINDINGSnWhen we compared high-titre and control groups, no difference in mortality between the first and the second vaccination was noted. After the second vaccination, the female-male mortality ratio was 1.84 (95% CI 1.19-2.84) in children in the high-titre groups who received DTP-IPV or IPV, and 0.59 (0.34-1.04) in controls who received standard measles vaccine (p=0.007). Children who received HTMV but no additional DTP-IPV or IPV had a female-male mortality ratio of 0.83 (0.41-1.67). This ratio was 2.22 (1.04-4.71) for children who received DTP-IPV after routine HTMV and 1.00 (0.68-1.47) for those who did not. When we combined the results from all trials, the female-male mortality ratio was 1.93 (1.33-2.81) for those who received DTP or IPV after HTMV, and 0.96 (0.69-1.34) for those who did not (p=0.006).nnnINTERPRETATIONnA change in sequence of vaccinations, rather than HTMV itself, may have been the cause of increased female mortality in these trials.

PREVALENCE OF AND MORTALITY FROM HUMAN IMMUNODEFICIENCY VIRUS TYPE 2 IN BISSAU, WEST AFRICA

In a community based prevalence study of HIV infection in Bissau, West Africa, 1987, the population in 100 randomly selected houses was asked to participate. 89% (1329/1499) were examined and had a blood sample taken. None was HIV-1 seropositive but 4.7% were seropositive for HIV-2 (0.6% in children, 8.9% in those aged 15 years and over, and 20% in those aged 40 years and over). There was no significant difference in seroprevalence between areas or ethnic groups or between individuals of different civil status when age was taken into account. Sexual contact and blood transfusions were the dominant transmission routes, and no case of vertical transmission was identified. The HIV-2 seroprevalence in spouses of HIV-2 seropositive index persons was 40%. For a history of blood transfusion the relative risk of being HIV-2 seropositive was 103.6 in children and 2.4 for adults. After exclusion of spouses, no clustering of HIV-2 seropositivity was seen. At follow-up, after a mean observation time of 325 days, there was an excess mortality for HIV-2 seropositives. The relative risk of dying for HIV-2 seropositive children was 60.8 and for adults 5.0.

Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate

In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4 months of age and the standard Schwarz vaccine from 9 months of age. Children were followed to the age of at least 3 years. The mortality ratio of the EZ vaccinees compared with control subjects was 1.79 (range, 1.06 to 3.02; p = 0.027) if children were excluded at the time of migration; if deaths after migration were included, the mortality ratio was 1.53 (range, 0.94 to 2.49; p = 0.087). Girls in the EZ group had significantly higher mortality rates than girls in the control group (mortality ratio = 1.95; range, 1.07 to 3.56; p = 0.027); there was no difference for the boys (mortality ratio = 0.98; range, 0.41 to 2.30). Adjustment for background factors in a Cox regression model did not modify these estimates. Furthermore, female recipients of EZ vaccine had more days with diarrhea (relative risk = 1.35; range, 1.17 to 1.56; p = 0.00003) and were more likely than control subjects to visit a health center in the month after vaccination (relative risk = 1.86; range, 1.05 to 3.31; p = 0.027); those who consulted were more likely to die subsequently (mortality ratio = 2.31; range, 0.99 to 5.41; p = 0.054). These observations were unplanned and require confirmation in larger studies.

The molecular epidemiology of varicella-zoster virus: Evidence for geographic segregation

Of 75 varicella-zoster virus (VZV) isolates obtained from patients in Africa, Asia, and the Far East, 74 (98.6%) were found to be positive for a BglI restriction site in gene 54. By contrast, <22% of strains from patients in the United Kingdom and in North and South America were positive for the BglI restriction site. Viruses positive for BglI were significantly more common in zoster occurring in patients of nonwhite origin (P<.05). Irrespective of the country in which the sample was obtained, 98% of strains positive for BglI clustered within a single phylogenetic group, which we termed group A; the exception was 1 strain that appeared to be recombinant genotype C/A. We used the BglI site to examine both the spread of type A viruses in the United Kingdom and the patterns of VZV infections within persons from different ethnic groups who grew up in the United Kingdom or abroad.

Clinical assessment and treatment in paediatric wards in the north-east of the United Republic of Tanzania

OBJECTIVEnWe assessed paediatric care in the 13 public hospitals in the north-east of the United Republic of Tanzania to determine if diagnoses and treatments were consistent with current guidelines for care.nnnMETHODSnData were collected over a five-day period in each site where paediatric outpatient consultations were observed, and a record of care was extracted from the case notes of children on the paediatric ward. Additional data were collected from inspection of ward supplies and hospital reports.nnnFINDINGSnOf 1181 outpatient consultations, basic clinical signs were often not checked; e.g. of 895 children with a history of fever, temperature was measured in 57%, and of 657 of children with cough or dyspnoea only 57 (9%) were examined for respiratory rate. Among 509 inpatients weight was recorded in the case notes in 250 (49%), respiratory rate in 54 (11%) and mental state in 47 (9%). Of 206 malaria diagnoses, 123 (60%) were with a negative or absent slide result, and of these 44 (36%) were treated with quinine only. Malnutrition was diagnosed in 1% of children admitted while recalculation of nutritional Z-scores suggested that between 5% and 10% had severe acute malnutrition; appropriate feeds were not present in any of the hospitals. A diagnosis of HIV-AIDS was made in only two cases while approximately 5% children admitted were expected to be infected with HIV in this area.nnnCONCLUSIONnClinical assessment of children admitted to paediatric wards is disturbingly poor and associated with missed diagnoses and inappropriate treatments. Improved assessment and records are essential to initiate change, but achieving this will be a challenging task.

Live Vaccine Against Measles, Mumps, and Rubella and the Risk of Hospital Admissions for Nontargeted Infections

IMPORTANCEnIn low-income countries, live measles vaccine reduces mortality from causes other than measles infection. Such nonspecific effects of vaccines might also be important for the health of children in high-income settings.nnnOBJECTIVEnTo examine whether the live vaccine against measles, mumps, and rubella (MMR) is associated with lower rates of hospital admissions for infections among children in Denmark.nnnDESIGN, SETTING, AND PARTICIPANTSnPopulation-based cohort study of Danish children born 1997-2006 and followed up from ages 11 months to 2 years (last follow-up, August 31, 2008). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months.nnnMAIN OUTCOMES AND MEASURESnIncidence rate ratios (IRRs) of hospital admissions for any infection, comparing receipt of MMR vs DTaP-IPV-Hib as the most recent vaccine. Risks, risk difference, and number needed to vaccinate were calculated for receiving MMR on time.nnnRESULTSnThe study included 495,987 children contributing with 56,889 hospital admissions for any type of infection during 509,427 person-years (rate, 11.2 per 100 person-years). For the 456,043 children who followed the recommended schedule and received MMR after the third dose of DTaP-IPV-Hib, MMR (rate, 8.9 per 100 person-years) vs the third dose of DTaP-IPV-Hib (rate, 12.4 per 100 person-years) as the most recent vaccine was associated with an adjusted IRR of 0.86 (95% CI, 0.84-0.88) for any admission for infection. There were 19,219 children immunized out of sequence. The adjusted IRR was 0.87 (95% CI, 0.80-0.95) for those receiving MMR (rate, 9.9 per 100 person-years) after the second dose of DTaP-IPV-Hib (rate, 15.1 per 100 person-years). However, in the 1981 children who subsequently received the third dose of DTaP-IPV-Hib (rate, 12.8 per 100 person-years) after MMR, the IRR for hospital admissions for infection was significantly greater (adjusted IRR, 1.62 [95% CI, 1.28-2.05]). The risk of admission for an infection between ages 16 months and 24 months was 4.6% (95% CI, 4.5%-4.7%) for receiving MMR on time and 5.1% (95% CI, 5.0%-5.2%) for not receiving MMR on time. The risk difference was 0.5 percentage point (95% CI, 0.4-0.6), and the number needed to vaccinate with MMR before age 16 months to prevent 1 admission for any infection was 201 (95% CI, 159-272).nnnCONCLUSIONS AND RELEVANCEnIn a cohort of Danish children, receipt of live MMR vs inactivated DTaP-IPV-Hib as the most recent vaccine was associated with a lower rate of hospital admissions for any infections. These findings require replication in other high-income populations.

TRIAL OF HIGH-DOSE EDMONSTON-ZAGREB MEASLES VACCINE IN GUINEA-BISSAU: PROTECTIVE EFFICACY

In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine.

Tuberculin Reaction, BCG Scar, and Lower Female Mortality.

Background: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. Methods: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. Results: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0–1 mm) was 0.54 (95% confidence interval = 0.30–0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31–0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11–0.88) among girls and 0.84 (0.39–1.82) among boys; and for BCG scar, the results were 0.41 (0.21–0.82) and 0.88 (0.34–2.30), respectively. Conclusions: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.

Varicella in Europe—A review of the epidemiology and experience with vaccination

There is no consensus as regards the European varicella immunisation policy; some countries have introduced varicella vaccination in their routine childhood immunisation programs whereas others have decided against or are debating. With the aim of providing an overview of the epidemiology of varicella in Europe and addressing the different strategies and the experiences so far, we performed a review of epidemiological studies done in Europe from 2004 to 2014. Varicella is mainly a disease of childhood, but sero-epidemiological studies show regional differences in the proportion of susceptible adults. Hospitalisation due to varicella is not common, but complications and hospitalisation mainly affect previously healthy children, which underlines the importance of not dismissing varicella as a disease of little importance. The experience with universal vaccination in Europe shows that vaccination leads to a rapid reduction of disease incidence. Vaccine effectiveness is high and a protective herd effect is obtained. Experience with vaccination in Europe has not been long enough, though, to draw conclusions on benefits and drawbacks with vaccination as well as the capacity for national programs in Europe to maintain a sufficiently high coverage to prevent a change in age group distribution to older children and young adults or on the impact that varicella immunisation may have on the epidemiology of shingles.

Conflicting priorities: evaluation of an intervention to improve nurse-parent relationships on a Tanzanian paediatric ward

BackgroundPatient, or parent/guardian, satisfaction with health care provision is important to health outcomes. Poor relationships with health workers, particularly with nursing staff, have been reported to reduce satisfaction with care in Africa. Participatory research approaches such as the Health Workers for Change initiative have been successful in improving provider-client relationships in various developing country settings, but have not yet been reported in the complex environment of hospital wards. We evaluated the HWC approach for improving the relationship between nurses and parents on a paediatric ward in a busy regional hospital in Tanzania.MethodsThe intervention consisted of six workshops, attended by 29 of 31 trained nurses and nurse attendants working on the paediatric ward. Parental satisfaction with nursing care was measured with 288 parents before and six weeks after the workshops, by means of an adapted Picker questionnaire. Two focus-group discussions were held with the workshop participants six months after the intervention.ResultsDuring the workshops, nurses demonstrated awareness of poor relationships between themselves and mothers. To tackle this, they proposed measures including weekly meetings to solve problems, maintain respect and increase cooperation, and representation to administrative forces to request better working conditions such as equipment, salaries and staff numbers. The results of the parent satisfaction questionnaire showed some improvement in responsiveness of nurses to client needs, but overall the mean percentage of parents reporting each of 20 problems was not statistically significantly different after the intervention, compared to before it (38.9% versus 41.2%). Post-workshop focus-group discussions with nursing staff suggested that nurses felt more empathic towards mothers and perceived an improvement in the relationship, but that this was hindered by persisting problems in their working environment, including poor relationships with other staff and a lack of response from hospital administration to their needs.ConclusionThe intended outcome of the intervention was not met. The priorities of the intervention – to improve nurse-parent relationships – did not match the priorities of the nursing staff. Development of awareness and empathy was not enough to provide care that was satisfactory to clients in the context of working conditions that were unsatisfactory to nurses.