YouBelong Home: A Ugandan Community Mental Health Intervention.

In Uganda, low resources for mental health provision combine with disadvantage and inadequate supports for family and community-based care. Catalysed by the need to reduce overcrowded psychiatric hospital wards and frequent readmissions at Butabika National Referral Mental Hospital (BNRMH) in Kampala, the nongovernment organisation YouBelong Uganda (YBU) developed the YouBelong Home (YBH) intervention. YBH is a theoretically eclectic pre and post hospital discharge intervention. This paper reports on qualitative findings of the project Curtailing Hospital Readmissions for Patients with Severe Mental Illness in Africa (CHaRISMA), which explored how to refine the YBH intervention. The project was funded by a UK Joint Global Health Trials (JGHT) Development Grant. Data was collected through structured interviews with service users and caregivers, reflective practice by the YBH implementing team and a stakeholder focus group. A summary of refinements to the YBH intervention follows the TIDieR format (Template for Intervention Description and Replication).

Allele-specific antibodies to Plasmodium falciparum merozoite surface protein-2 and protection against clinical malaria.

IgG and IgG3 antibodies to merozoite surface protein-2 (MSP-2) of Plasmodium falciparum have been associated with protection from clinical malaria in independent studies. We determined whether this protection was allele-specific by testing whether children who developed clinical malaria lacked IgG/IgG3 antibodies specific to the dominant msp2 parasite genotypes detected during clinical episodes. We analysed pre-existing IgG and IgG1/IgG3 antibodies to antigens representing the major dimorphic types of MSP-2 by ELISA. We used quantitative real-time PCR to determine the dominant msp2 alleles in parasites detected in clinical episodes. Over half (55%, 80/146) of infections contained both allelic types. Single or dominant IC1- and FC27-like alleles were detected in 46% and 42% of infections respectively, and both types were equally dominant in 12%. High levels of IgG/IgG3 antibodies to the FC27-like antigen were not significantly associated with a lower likelihood of clinical episodes caused by parasites bearing FC27-like compared to IC1-like alleles, and vice versa for IgG/IgG3 antibodies to the IC1-like antigen. These findings were supported by competition ELISAs which demonstrated the presence of IgG antibodies to allele-specific epitopes within both antigens. Thus, even for this well-studied antigen, the importance of an allele-specific component of naturally acquired protective immunity to malaria remains to be confirmed.

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 2. Mortality and morbidity from malaria in the study area.

Background data on child mortality and morbidity from malaria were obtained in a new study area in the centre of The Gambia, south of the river, chosen as the site for a malaria intervention trial. Infant and child mortality rates were 120 and 41 per 1000 respectively. Results obtained using post-mortem questionnaires suggested that malaria was an uncommon cause of death in children under the age of one year but responsible for about 40% of deaths in children aged 1-4 years. Ninety-two percent of deaths attributed to malaria occurred during or immediately after the rainy season. Parasite and spleen rates in children aged 1-5 years at the end of the malaria transmission season were 66% and 64% respectively. Malariometric indices were similar in primary health care (PHC) villages, selected as sites for an intervention with insecticide-treated bed nets and targeted chemoprophylaxis, and in smaller, non-PHC, control villages.

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 6. The impact of the interventions on mortality and morbidity from malaria.

The effects of insecticide-impregnated bed nets on mortality and morbidity from malaria have been investigated during one malaria transmission season in a group of rural Gambian children aged 6 months to 5 years. Sleeping under impregnated nets was associated with an overall reduction in mortality of about 60% in children aged 1-4 years. Mortality was not reduced further by chemoprophylaxis with Maloprim given weekly by village health workers throughout the rainy season. Episodes of fever associated with malaria parasitaemia were reduced by 45% among children who slept under impregnated nets. The addition of chemoprophylaxis provided substantial additional benefit against clinical attacks of malaria; 158 episodes were recorded among 946 children who slept under impregnated nets but who also received chemoprophylaxis. Chemoprophylaxis reduced the prevalence of splenomegaly and parasitaemia at the end of the malaria transmission season by 63% and 83% respectively. Thus, insecticide-impregnated bed nets provided significant protection in children against overall mortality, mortality attributed to malaria, clinical attacks of malaria, and malaria infection. The addition of chemoprophylaxis provided substantial additional protection against clinical attacks of malaria and malaria infection but not against death.

Data management for an efficacy trial of a vaccine in the Gambia.

An individually randomised double-blind trial of PRP-T Hib conjugate vaccine was conducted in the Gambia between 1993 and 1995, in which 42,848 children were randomised into one of 10 groups, five corresponding to vaccine and five to placebo. Basic demographic data were collected on all children, and administration details of all doses of EPI vaccines were recorded. In addition, details on all doses of vaccines were recorded on each child's home-based health card; 2,681 episodes of possible Hib disease were investigated and for each episode detailed clinical data were collected. These investigations yielded 50 cases of confirmed Hib disease, which formed the basis of the final efficacy results. In all 50 cases, the data on the children's health card, describing the doses of study vaccine received exactly, matched the vaccination database which was filled with data returned from the clinics. The data-management procedures are described in detail in this paper.

Risk factors for persisting neurological and cognitive impairments following cerebral malaria.

BACKGROUND: Persisting neurological and cognitive impairments are common after cerebral malaria. Although risk factors for gross deficits on discharge have been described, few studies have examined those associated with persistent impairments. METHODS: The risk factors for impairments following cerebral malaria were determined by examining hospital records of 143 children aged 6-9 years, previously admitted with cerebral malaria, who were assessed at least 20 months after discharge to detect motor, speech and language, and other cognitive (memory, attention, and non-verbal functioning) impairments. RESULTS: The median age on admission was 30 months (IQR 19-42) and the median time from discharge to assessment was 64 months (IQR 40-78). Thirty four children (23.8%) were defined as having impairments: 14 (9.8%) in motor, 16 (11.2%) in speech and language, and 20 (14.0%) in other cognitive functions. Previous seizures (OR 5.6, 95% CI 2.0 to 16.0), deep coma on admission (OR 28.8, 95% CI 3.0 to 280), focal neurological signs observed during admission (OR 4.6, 95% CI 1.1 to 19.6), and neurological deficits on discharge (OR 4.5, 95% CI 1.4 to 13.8) were independently associated with persisting impairments. In addition, multiple seizures were associated with motor impairment, age <3 years, severe malnutrition, features of intracranial hypertension, and hypoglycaemia with language impairments, while prolonged coma, severe malnutrition, and hypoglycaemia were associated with impairments in other cognitive functions. CONCLUSIONS: Risk factors for persisting neurological and cognitive impairments following cerebral malaria include multiple seizures, deep/prolonged coma, hypoglycaemia, and clinical features of intracranial hypertension. Although there are overlaps in impaired functions and risk factors, the differences in risk factors for specific functions may suggest separate mechanisms for neuronal damage. These factors could form the basis of future preventive strategies for persisting impairments.

Socioeconomic inequalities in childhood mortality: the 1970s to the 1980s.

The last three decades have witnessed substantial reductions in childhood mortality in most developing nations. Despite this encouraging picture, analysis of WFS and DHS survey data shows that socioeconomic disparities in survival chances have not narrowed between the 1970s and 1980s, and in some cases, have widened. Changes in mother's education and father's occupation contributed only modestly to secular declines in mortality. In most countries studied, no more than 20 per cent of the national trend could be accounted for by compositional improvements. The median contributions of improvements in mother's education and father's occupation were ten and eight per cent, respectively.

PIP: World Fertility Survey (WFS) and Demographic Health Survey (DHS) data are the basis for the description of declines in mortality between 1965-85 and the examination of the extent to which declines are attributed to improvement in socioeconomic structure in Senegal, Egypt, Indonesia, Peru, Morocco, Dominican Republic, Ecuador, Tunisia, Sudan (North), Thailand, Mexico, and Colombia. The analytical design is briefly described as the calculation of measures of mortality at the national level and for subgroups and defined in terms of maternal education, paternal occupation/education, and rural/urban residence. Trends were calculated from estimates for different periods. Trends were calculated form estimates for different periods. Absolute and relative differences for subgroups were assessed at several points in time to express differential mortality. The consistency and reliability of WFS and DHS data are discussed and conclusions drawn that only general patterns are expressed; mortality trends are not known with certainty and caution is urged in the interpretation. Results are presented for national levels and trends in childhood mortality, socioeconomic composition and national trends, and socioeconomic inequalities in childhood mortality: convergence and polarization. The main findings are that all but 1 of the 12 countries experienced mortality declines of around 50% from 1965 to 1985. The declines in mortality at 1-5 years was steeper than for infant mortality at 1-5 years was steeper than for infant mortality. The level of mortality in 1965 was not a factor in the improvement in child survival over the 20-year period; i.e., countries such as Thailand, Mexico, and Colombia with low levels of mortality in 1965 had proportionate increases equal to high mortality countries such as Egypt and Indonesia. The pace of decline has accelerated since the mid-1970s. Compositional change in, for instance, educational attainment, occupational structure, or level of urbanization, had not contributed substantially to mortality decline in the 12 countries, i.e., 20-35% of national decline could be attributed to improvements in maternal education in all but 1 country. Huge inequalities have persisted throughout the decades, although all socioeconomic levels have benefited form the improvement in survival. Other literature suggests that response to illness may be more important than prevention in explaining survival differentials in different socioeconomic subgroups, and future detailed analysis is warranted.

Implementing a nationwide insecticide-impregnated bednet programme in The Gambia.

Earlier studies in The Gambia suggested that the use of impregnated bednets might prove to be a useful malaria control strategy. Based on the results of these studies, in 1992 the Government of The Gambia was encouraged to initiate a National Impregnated Bednet Programme (NIBP) as part of the National Malaria Control Programme Strategy. This paper describes the implementation process/procedure of the NIBP. Evaluation results showed that, overall, 83% of the bednets surveyed has been impregnated, and 77% of children under the age of five years and 78% of women of childbearing age were reported to be sleeping under impregnated bednets.

PIP: On the basis of pilot studies indicating that bednets impregnated with the insecticide Permethrin are an effective, acceptable method of malaria control, the Gambian government introduced the National Impregnated Bednet Program (NIBP) in 1992. Implementation activities included sensitization sessions with government officials, representatives of nongovernmental organizations, local health care workers, and village leaders; an IEC campaign involving posters, t-shirts, radio programming, and a videotape; staff training; and supply ordering and distribution. A compound-by-compound impregnation strategy was used, and women were instructed not to wash the nets until the end of the rainy season (5 months). At the end of 5 months, a cross-sectional survey involving 6 compounds in 221 villages was conducted. Overall bednet use was 73%, while that for bednet impregnation was 83%. 77% of children under 5 years old and 78% of women of childbearing age (those at greatest risk of malaria) were sleeping under impregnated nets in program villages. During the first year of the intervention, a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages. Although the insecticide was provided free of charge by the government, continued subsidy is not feasible and some form of cost recovery must be developed.

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion.

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

A pilot safety and immunogenicity study of the malaria vaccine SPf66 in Gambian infants.

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been undertaken in 150 Gambian infants. No significant systemic side effects were recorded but modest local reactions were seen after the administration of a third 1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a 0.5 mg dose. However, antibody levels fell rapidly after administration of the third dose of vaccine and showed little change over the following malaria transmission season. The incidence of clinical malaria was higher among children who received SPf66 than among children who received inactivated polio vaccine, the effect being most marked among children who received 1.0 mg Colombian SPf66. As the trial was not designed to measure the effect of SPf66 on morbidity from malaria, the significance of this finding is uncertain.

The effect of insecticide-treated bed nets on mortality of Gambian children.

Insecticide treatment of bed nets ("mosquito nets") may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria. In a rural area of The Gambia, bed nets in villages participating in a primary health-care (PHC) scheme were treated with permethrin at the beginning of the malaria transmission season. Additionally, children aged 6 months to 5 years were randomised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season. We measured mortality in children in PHC villages before and after the interventions described, and compared this with mortality in villages where no interventions occurred (non-PHC villages). About 92% of children in PHC villages slept under insecticide-treated bed nets. In the year before intervention, mortality in children aged 1-4 years was lower in non-PHC villages. After intervention, the overall mortality and mortality attributable to malaria of children aged 1-4 in the intervention villages was 37% and 30%, respectively, of that in the non-PHC villages. Among children who slept under treated nets, we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths. Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria.

Efficacy trial of malaria vaccine SPf66 in Gambian infants.

SPf66 malaria vaccine is a synthetic protein with aminoacid sequences derived from pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. SPf66 was found to have a 31% protective efficacy in an area of intensive malaria transmission in Tanzanian children, 1-5 years old. We report a randomised, double-blind, placebo-controlled trial of SPf66 against clinical P falciparum malaria in Gambian infants. 630 children, aged 6-11 months at time of the first dose, received three doses of SPf66 or injected polio vaccine (IPV). Morbidity was monitored during the following rainy season by means of active and passive case detection. Cross-sectional surveys were carried out at the beginning and at the end of the rainy season. An episode of clinical malaria was defined as fever (> or = 37.5 degrees C) and a parasite density of 6000/microL or more. Analysis of efficacy was done on 547 children (316 SPf66/231 IPV). No differences in mortality or in health centre admissions were found between the two groups of children. 347 clinical episodes of malaria were detected during the three and a half months of surveillance. SPf66 vaccine was associated with a protective efficacy against the first or only clinical episode of 8% (95% CI -18 to 29, p = 0.50) and against the overall incidence of clinical episodes of malaria of 3% (95% CI -24 to 24, p = 0.81). No significant differences in parasite rates or in any other index of malaria were found between the two groups of children. The findings of this study differ from previous reports on SPf66 efficacy from South America and from Tanzania. In The Gambia, protection against clinical attacks of malaria during the rainy season after immunisation in children 6-11 months old at time of the first dose was not achieved.

PIP: During December 1993 to November 1994, in the Upper River Division of The Gambia, 630 infants aged 6-11 months at time of first dose received three doses of malaria vaccine SPf66 or injected polio vaccine (IPV) and were followed up at home during the rainy season using active and passive case detection methods to determine the protective efficacy of SPf66 against clinical episodes of malaria due to Plasmodium falciparum. The researchers were able to use data on only 547 children (316 SPf66/231 IPV) to determine efficacy. The definition of clinical malaria was fever (37.5 degrees Celsius or higher) and a parasite density of at least 6000/mcl. The two groups were essentially the same in terms of mortality, health center admissions, parasite rates, or any other index of malaria. Health workers identified 347 clinical episodes of malaria during the three months of surveillance. SPf66 vaccine had a protective efficacy against first or only clinical episode of malaria of 8% (p = 0.5). Its protective efficacy was 3% against all clinical episodes of malaria. The results of this trial were different than those from earlier reports on SPf66 efficacy from South America and Tanzania. Possible reasons accounting for the different findings were a mistake in coding syringes for the third dose, substantially less intensity of malaria infection in The Gambia than South America, younger children in The Gambia than in Tanzania, genetic differences in the populations, and difference in length of follow-up. In conclusion, protection against malaria during the rainy season after immunization with SPf66 vaccine in infants aged 6-11 months did not occur.