Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial.

BACKGROUND: If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS: Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS: Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS: Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION: ISRCTN58046240.

Perceptions of the usefulness of external support to immunization coverage in Guinea-Bissau: a Delphi analysis of the GAVI-Alliance cash-based support.

INTRODUCTION: Although many countries have improved vaccination coverage in recent years, some, including Guinea-Bissau, failed to meet expected targets. This paper tries to understand the main barriers to better vaccination coverage in the context of the GAVI-Alliance (The Global Alliance for Vaccines and Immunisation) cash-based support provided to Guinea-Bissau. METHODS: The analysis is based on a document analysis and a three round Delphi study with a final consensus meeting. RESULTS: Consensus attributed about 25% of the failure to perform better to implementation problems; and about 10% to governance and also 10% to scarce resources. The qualitative analysis validates the importance of implementation issues and upgraded the relevance of the human resources crisis as an important drawback. The recommendations were balanced in their upstream-downstream focus but were blind to health information issues and logistical difficulties. CONCLUSIONS: It is commendable that such a fragile state, with all sorts of barriers, manages to sustain a slow steady growth of its vaccination coverage. Not reaching the targets set reflects the inappropriateness of those targets rather than a lack of commitment of the health workforce. In the unstable context of countries such as Guinea-Bissau, the predictability of the funds from global health initiatives like the GAVI-Alliance seem to make all the difference in achieving small consistent health gains even in the presence of other major bottlenecks.

Perceptions of the usefulness of external support to immunization coverage in Guinea-Bissau: a Delphi analysis of the GAVI-Alliance cash-based support

INTRODUCTION: Although many countries have improved vaccination coverage in recent years, some, including Guinea-Bissau, failed to meet expected targets. This paper tries to understand the main barriers to better vaccination coverage in the context of the GAVI-Alliance (The Global Alliance for Vaccines and Immunisation) cash-based support provided to Guinea-Bissau. METHODS: The analysis is based on a document analysis and a three round Delphi study with a final consensus meeting. RESULTS: Consensus attributed about 25% of the failure to perform better to implementation problems; and about 10% to governance and also 10% to scarce resources. The qualitative analysis validates the importance of implementation issues and upgraded the relevance of the human resources crisis as an important drawback. The recommendations were balanced in their upstream-downstream focus but were blind to health information issues and logistical difficulties. CONCLUSIONS: It is commendable that such a fragile state, with all sorts of barriers, manages to sustain a slow steady growth of its vaccination coverage. Not reaching the targets set reflects the inappropriateness of those targets rather than a lack of commitment of the health workforce. In the unstable context of countries such as Guinea-Bissau, the predictability of the funds from global health initiatives like the GAVI-Alliance seem to make all the difference in achieving small consistent health gains even in the presence of other major bottlenecks.

Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country.

BACKGROUND: Most developing countries are implementing the WHO immunisation programme. Although vaccines reach most children, many modifications of the recommended schedule are observed in practice. We investigated the association between vaccination status and risk of hospitalisation in Guinea-Bissau. METHODS: From May 2003 to May 2004, all consultations of children less than five years of age at the outpatient clinic of the paediatric ward at the national hospital in Bissau were registered. For each consultation, information was collected about the child's name, sex, age and socio-cultural conditions, as well as diagnosis and whether the child was hospitalised. Information about vaccinations was also registered from the child's vaccination card. We analysed the association between vaccination status and risk of hospitalisation in age intervals according to the pre-dominant vaccines. We particularly emphasised the comparison of those who had received the recommended vaccination for the age groups and those who were delayed and only had the previous vaccinations. We also examined those who had received the vaccines out of sequence. RESULTS: Information about vaccinations was available for 11,949 outpatient children of whom 2219 (19%) were hospitalised. Among children less than 3 months of age, unvaccinated children compared to BCG children had as expected a higher risk of hospitalisation; controlled for important determinants of hospitalisation, the hospitalisation risk ratio (HRR) was 1.99 (95% CI 1.37-2.89). In contrast, there was no difference in the HRR for children aged 1½-8 months who were delayed and had only received BCG compared to those who as recommended had received diphtheria-tetanus-pertussis (DTP) vaccine after BCG (HRR=1.10 (0.77-1.59)). In the age interval 9-17 months of age, children who were delayed and had only received DTP had significantly higher risk of hospitalisation compared with children who as recommended had measles vaccine (MV) as the most recent vaccination (HRR=1.39 (1.16-1.66)). Having received DTP after MV (HRR=1.60 (1.15-2.24)) or MV and DTP simultaneously (HRR=1.51 (1.16-1.97)) was also associated with higher risk than MV only as most recent vaccination. In contrast, the children aged 18-59 months who as recommended had received a DTP booster after MV did not have lower risk of hospitalisations compared with children who were delayed and had received only MV (RR=0.90 (0.75-1.07)). After 9 months of age, there was a significant difference in the female-male HRR for children who had MV (HRR=0.85 (0.72-1.00)) or DTP (HRR=1.08 (0.96-1.22)) as most recent vaccination (p=0.02, test of interaction). CONCLUSION: Following the recommended vaccination schedule for BCG and MV is associated with a reduced risk of hospitalisation but this is not the case for DTP and booster DTP. Receiving DTP simultaneously with MV or after MV is associated with increased risk of hospitalisation. Vaccines have sex-differential effects on the risk of hospitalisation.

Sex differences in the effect of vaccines on the risk of hospitalization due to measles in Guinea-bissau.

BACKGROUND: Routine immunizations have non-specific and sex-differential effects on childhood mortality and morbidity in low-income countries; BCG and measles vaccine (MV) may reduce and diphtheria-tetanus-pertussis vaccine (DTP) may increase the mortality of girls relative to boys. SETTING: Urban area in Guinea-Bissau, with a demographic surveillance system and registration of all pediatric hospitalizations. Guinea-Bissau experienced a large outbreak of measles infection in 2003-2004. DESIGN: We used hospital and community data to examine the impact of other vaccines on the risk of hospitalizations for measles infection. Vaccine efficacy (VE) against hospitalization for children aged 6 to 59 months of age was examined. We assessed whether VE depended on vaccination status for other vaccines and whether the pattern differed for boys and girls. MAIN OUTCOME MEASURE: Sex-specific vaccine efficacy against hospitalization for children aged 6 to 59 months of age. RESULTS: The VE depended on sex and the sequence of vaccinations. The VE of MV against hospitalization for measles was better for girls than for boys. Among children who had received MV as the most recent vaccine VE against hospitalization was as high as 96% for girls, but only 81% for boys (P = 0.002). Among children who had received DTP simultaneously with MV or DTP after MV, VE declined for girls (91%) and increased for boys (90%). Compared with having received MV as most recent vaccination, DTP simultaneously with MV or DTP after MV improved the efficacy significantly for boys and the effect was significantly different for boys and girls (P = 0.023). The female-male risk ratio of hospitalization varied significantly, depending on the most recent vaccination (P = 0.014); it was 0.28 (0.11-0.68) for MV alone, but 1.21 (0.82-1.77) for DTP but no MV, and 1.13 (0.58-2.18) for DTP simultaneously with MV or after MV. Among MV-unvaccinated children, BCG-vaccinated girls had a lower risk of measles hospitalization than DTP-vaccinated girls (RR=0.0 (0.0-0.99), exact test).

Hypothermia of newborns is associated with excess mortality in the first 2 months of life in Guinea-Bissau, West Africa.

OBJECTIVE: To examine the long-term effects of neonatal hypothermia (HT) on survival. METHODS: Using the longitudinal community and hospital surveillance system of the Bandim Health Project, we followed children born between 1997 and 2002 at the only maternity ward in the city. All children's axillary temperature was measured within 12 h of birth. They were followed from birth to 6 months of life through regular home visits. RESULTS: We identified 2926 live births in the study area and 177 deaths before 6 months of age. Based on mortality risk, we defined a temperature below 34.5 degrees C as the cut-off point for HT. Two hundred and thirty-eight (8%) children had HT. Controlled for birth weight, HT was associated with a nearly fivefold increase in mortality during the first 7 days of life [mortality ratio (MR) = 4.81 (2.90-8.00)] and with increased mortality from 8 to 56 days of life [MR = 2.55 (1.29-5.04)]. CONCLUSION: HT is associated with excess mortality beyond the perinatal period up to at least 2 months of age, especially among low-birth-weight children. Hence, failure to comply with the WHO guidelines for care of newborns in low-income countries may have long-term consequences for child survival which have not previously been assessed. The WHO definition of HT should be based on mortality data.

Promotion of exclusive breastfeeding is not likely to be cost effective in West Africa. A randomized intervention study from Guinea-Bissau.

AIM: To evaluate the impact of promotion of exclusive breastfeeding on infant health in Guinea-Bissau, West Africa, where mortality rates are high, breastfeeding is widely practiced but exclusive breastfeeding is rare. METHOD: At the Bandim Health Project in Guinea Bissau, West Africa, a birth cohort of 1721 infants were randomized to receive health education: promotion of exclusive breastfeeding for the first 4-6 months of life according to WHO recommendations at the time of the study. All children were followed from birth to 6 months of age. RESULTS: Introduction of both water and weaning food was significantly delayed in the intervention group. However we found no beneficial health effects of the intervention; there was no reduction in mortality in the intervention group compared with the control group (mortality rate ratio: 1.86 (0.79-4.39)), weight at 4-6 months of age was significantly lower in the intervention group (7.10 kg vs. 7.25 kg; Wilcoxon two-sample test: p=0.03). There was no difference in diarrhoea morbidity and hospitalization rates. CONCLUSION: Although mothers were sensitive to follow new breastfeeding recommendations, it had no beneficial impact on infant health in this society with traditional, intensive breastfeeding. There seems to be little reason to discourage local practices as long as there are no strong data justifying such a change.

Increased mortality in the year following discharge from a paediatric ward in Bissau, Guinea-Bissau.

BACKGROUND: Few studies in developing countries have examined posthospital mortality and little is known about the magnitude of posthospital mortality and risk factors for long-term survival. A better understanding of the determinants of posthospital mortality could help improve discharge policies and interventions with implications for overall childhood mortality. STUDY POPULATION: In the period from 1991 to 1996 all paediatric admissions coming from the Bandim Health Project's area were registered at the National Hospital in Bissau, Guinea-Bissau. Posthospitalization information from a population-based surveillance system was available for 4153 admissions contributed by 3373 individuals having between 1 and 8 admissions during the period. Three thousand six hundred forty seven (3647) admissions by 2950 children resulted in live discharges. Postdischarge mortality included all deaths during 1 year following live discharge. RESULTS: Among the 221 children who died during the first year after discharge, 170 died in the community and 51 children died during a subsequent hospitalization; thirty-eight died on the day of discharge and almost one third had died within the first 2 weeks. The overall in-hospital and 12-month posthospital mortality was 20%. Compared to the mortality level in the community and controlled for other determinants of childhood mortality, children discharged from hospital had 12 times higher risk of dying during the first 2 weeks after discharge. The mortality rate ratio (MR) was 6.2 (95% confidence interval 3.8-10.2) times higher when we excluded those who died at the day of discharge. For the period 30-91 days after discharge the MR ratio was 3.7 (2.5-5.5), and in the period 3-6 months after discharge, the risk estimate was still 2.5 (1.6-3.9) times higher than community mortality. In a multivariate analysis, the all-dominating risk factor was discharge status as 'fled' in the sense of nonmedical discharge, the MRs being 18.6 (9.5-36.6) in the first 2 weeks after discharge and 4.0 (2.0-8.3) in the remaining part of the first year. Other significant risk factors for postdischarge mortality included ethnic group, housing quality and maternal education, and were similar to risk factors for community mortality. The same diagnoses that had high acute mortality, including anaemia, diarrhoea and 'other', were also associated with high postdischarge mortality. CONCLUSION: There was a marked increase in mortality after hospitalization, the effect being particularly strong for children who fled the hospital. Improved discharge and follow-up policies might have an important impact on survival after paediatric hospitalization. Studies on the effect of focused intervention at discharge are needed.

Reduced in-hospital mortality after improved management of children under 5 years admitted to hospital with malaria: randomised trial.

OBJECTIVE: To test whether strict implementation of a standardised protocol for the management of malaria and provision of a financial incentive for health workers reduced mortality. DESIGN: Randomised controlled intervention trial. SETTING: Paediatric ward at the national hospital in Guinea-Bissau. All children admitted to hospital with severe malaria received free drug kits. PARTICIPANTS: 951 children aged 3 months to 5 years admitted to hospital with a diagnosis of malaria randomised to normal or intervention wards. INTERVENTIONS: Before the start of the study, all personnel were trained in the use of the standardised guidelines for the management of malaria, including strict follow-up procedures. Nurses and doctors were randomised to work on intervention or control wards. Personnel in the intervention ward received a small financial incentive ($50 (25 pounds sterling; 35 euros)/month for nurses and $160 for doctors) and their compliance with standard case management was closely monitored. MAIN OUTCOME MEASURES: In-hospital mortality and cumulative mortality within 4 weeks of hospital admission. RESULTS: In-hospital mortality was 5% for the intervention group and 10% in the control group (risk ratio 0.48, 95% confidence interval 0.29 to 0.79). The effect may have been stronger in patients with positive malaria slides (0.36, 0.16 to 0.80). Cumulative mortality 4 weeks after discharge was also lower in the intervention group (0.61, 0.40 to 0.95). CONCLUSIONS: Supervising healthcare workers to adhere to a standardised treatment protocol was associated with greatly reduced in-hospital mortality. Financial incentives may be important for the dedication and compliance of staff members. TRIAL REGISTRATION: Clinical Trials NCT00465777 [ClinicalTrials.gov].

Persisting high hospital and community childhood mortality in an urban setting in Guinea-Bissau.

AIM: To describe paediatric hospitalization in a West African capital in relation to overall childhood mortality in the community and to evaluate the potential impact of improved management at the hospital. METHODS: Hospital data on child admissions in a 6-year period were linked to information in a community-based longitudinal surveillance system. Paediatric hospitalization rates, risk factors for hospitalizations, community mortality, in-hospital mortality and the proportion of deaths occurring at hospital were examined. RESULTS: Almost 15% of infants and 45% of children less than 5 years of age had been hospitalized, and 24% of all deaths in the community occurred in-hospital. Community infant and under-three mortality rates were 110 and 207 per 1,000 person-years, respectively. In-hospital mortality remained persistently high from 1991 to 1996 and the overall in-hospital mortality was 12%. It was found that wet season, lack of maternal schooling and living in a specific district were significant risk factors for both community and in-hospital death, whereas higher hospitalization rates were associated with better-off families. CONCLUSION: In populations with high hospitalization rates, even minor improvements in acute case management of sick children attending the hospital would be expected to result in substantial reduction in overall childhood mortality. Persistently high acute in-hospital mortality reflects the need of immediate and appropriate care at the hospital. Treatment should be free of charge, in order to minimize the impact of social inequality.

DTP with or after measles vaccination is associated with increased in-hospital mortality in Guinea-Bissau.

BACKGROUND: The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria-tetanus-pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine. SETTING: The only paediatric ward in Bissau, Guinea-Bissau. PARTICIPANTS: Children hospitalised during two periods in 1990-1996 and 2001-2002 who had received MV prior to hospitalisation. MAIN OUTCOME MEASURE: The all-cause case fatality at the hospital for children aged 6-17 months. RESULT: The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37-4.67) and 1.77 (0.92-3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34-3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. CONCLUSION: Administration of DTP with, or after MV, may reduce the beneficial effect of MV.

Routine vaccinations associated with divergent effects on female and male mortality at the paediatric ward in Bissau, Guinea-Bissau.

Several studies have suggested that routine childhood immunisations may have non-specific effects on mortality. To examine which disease categories might be affected, we investigated whether immunisation status had an impact on the case fatality for hospitalised children. Between 1990 and 1996, the Bandim Health Project maintained a register of all children from the study area hospitalised at the paediatric ward of the central hospital in Bissau, Guinea-Bissau. The study included 2079 hospitalised children aged 1.5-17 months coming from the Bandim study area. Among children whose vaccination card had been seen at admission, the case fatality ratio for measles-vaccinated children versus measles-unvaccinated children was 0.51 (0.27-0.98), the beneficial effect being significantly stronger for girls than for boys (test of interaction, p=0.050). The protective effect of measles vaccine remained unchanged when hospitalised measles cases were excluded from the analysis (0.49 (0.26-0.94)). The effect of measles vaccine was strongest for children with pneumonia (MR=0.28 (0.07-0.91)) and presumptive malaria (MR=0.40 (0.13-1.18)). For measles-vaccinated children, the female to male case fatality ratio was 0.54 (0.28-0.97). Among children having received diphtheria-tetanus-pertussis (DTP) and oral polio (OPV) as the last vaccines, girls had higher case fatality than boys, the mortality ratio being 1.63 (1.03-2.59). The female to male ratios were significantly inversed for DTP and OPV versus measles vaccine (test of interaction, p=0.003). These results remained unchanged if 1-month post-discharge deaths were included in the analysis, and in multivariate analyses controlling for determinants of mortality. In conclusion, measles vaccine was associated with reduced mortality from diseases other than measles, the beneficial effect being stronger for girls than for boys. On the other hand, DTP and OPV vaccine were associated with higher case fatality for girls than for boys. Understanding the divergent non-specific effects of common vaccines may contribute to better child survival in developing countries.

Oral polio vaccination and low case fatality at the paediatric ward in Bissau, Guinea-Bissau.

Oral polio vaccine (OPV) and diphtheria-tetanus-pertussis (DTP) vaccines are given simultaneously in routine immunisation programmes in developing countries. It is therefore difficult to determine the separate effects of these vaccines on survival. We used the shortage of DTP vaccine in Bissau to examine the impact of OPV on the case fatality at the paediatric ward in Bissau. For 719 children less than 5 years of age whose vaccination card had been seen at admission and who had not yet received measles vaccine, having received OPV only was associated with a case fatality of 6% compared with 15% for children having received combined DTP and OPV vaccinations, the case fatality ratio (CFR) being 0.29 (95% confidence interval (CI) 0.11-0.77). Even if children fleeing the hospital were assumed to have died shortly after leaving the hospital, the case fatality would still be lower for children having received OPV only (CFR = 0.41; (95% CI 0.20-0.81)). The tendency was similar for children hospitalised with pneumonia, diarrhoea, and presumptive malaria. Control for background factors had no impact on the estimate. In areas with high mortality, OPV administered alone may have non-specific beneficial effects or DTP may have a negative effect for children who had received both DTP and OPV.