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This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. Among colonized individuals, density decreased with increasing age. Time-trends analysis revealed that pneumococcal vaccination appeared to lower the density of nasopharyngeal carriage.Background. This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage.Methods. A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1–4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination.Results. Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non–vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT.Conclusions. A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis.Clinical Trials Registration. ISRCTN51695599. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2011; 17: 1600-1607 Abstract The development of an effective malaria vaccine has taken many decades, but there is now a good chance that the first malaria vaccine will be licensed within the next few years. However, this vaccine (RTS,S) will not be fully effective, and more efficacious, second-generation vaccines will be needed. Good progress is being made in the development of potential vaccines directed at each of the three main stages of the parasite's life cycle, with a variety of different approaches, but many challenges remain, e.g. overcoming the problem of polymorphism in many key parasite antigens. It is likely vaccines that are effective enough to block transmission, and thus contribute to increasing drives towards malaria elimination, will need to contain antigens from different stages of the parasite's life cycle. [ABSTRACT FROM AUTHOR]

Regular physical exercise is beneficial for both physical and mental health. By contrast, stress is associated with deleterious effects on health and there is growing evidence that regular physical exercise counteracts some of the effects of stress. However, most previous studies have suggested that prior exercise does not alter the acute hypothalamic pituitary adrenal (HPA) axis responses to stress. The present series of studies provides evidence that in rats, 6 weeks (but not 1 or 3 weeks) of voluntary wheel running reduces the HPA axis responses to lower-intensity stressors such as an i.p. saline injection, exposure to a novel environment or exposure to moderate intensity noise, but not to more intense stressors such as predator odour exposure or restraint. Daily exercise does not appear to be necessary for the reduction in HPA axis responses, with intermittent access (24 h out of each 72-h period) to a running wheel for 6 weeks, resulting in similar decrements in adrenocorticotrophic hormone and corticosterone release in response to 85 dBA noise exposure. Data from in situ hybridisation for c- fos mRNA are consistent with the hypothesis that voluntary exercise results in a decrease in HPA axis responsiveness to a low-intensity stressor at a central level, with no changes in primary sensory processing. Together, these data suggest that 6 weeks of daily or intermittent exercise constrains the HPA axis response to mild, but not more intense stressors, and that this regulation may be mediated at a central level beyond the primary sensory input. [ABSTRACT FROM AUTHOR]

An unexpectedly large reduction in the burden of malaria has recently been achieved in a number of malaria endemic countries following the scaling up of effective treatment and simple vector control programmes. These achievements question the need for a partially effective malaria vaccine targeted at disease prevention. If an anti-disease vaccine is to replace or supplement existing control measures a high level of efficacy, sustained over a number of years, will be required. Recent successes in malaria control have re-awakened interest in the possibility of malaria elimination in areas where this was not previously considered to be a feasible objective. Malaria vaccines with transmission-blocking properties could play a key role in future elimination programmes. [ABSTRACT FROM AUTHOR]

In view of the important protective role of the fetal membranes, wound sealing, tissue regeneration, or wound healing could be life saving in cases of preterm premature rupture of the membranes. Although many investigators are studying the causes of preterm premature rupture of membranes, the emphasis has not been on the wound healing capacity of the fetal membranes. In this review, the relevant literature on the pathophysiologic condition that leads to preterm premature rupture of membranes will be summarized to emphasize a continuum of events between rupture and repair. We will present the current knowledge on fetal membrane wound healing and discuss the clinical implications of these findings. We will critically discuss recent experimental interventions in women to seal or heal the fetal membranes after preterm premature rupture of membranes. [ABSTRACT FROM AUTHOR]

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Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1–4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54.1% and 37.3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/ 45 (r = 0.49, P < 0.001) and to a serological reaction with epitopes of the same molecule (r = 0.38, P = 0.003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0.29, P = 0.03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission-blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation. [ABSTRACT FROM AUTHOR]

We conducted a study of 1945 children and 2885 adults who presented with fever to a hospital outpatients clinic in an urban area of India order to develop and evaluate a clinical algorithm for the diagnosis of malaria. Only 139 (7%) children and 349 (12%) adults had microscopically confirmed malaria. None of the symptoms or signs elicited from the respondents were good predictors of clinical malaria. Simple scores were derived through combining clinical features which were associated with slide positivity or were judged by clinicians to be important. The best-performing algorithms were a score of 4 clinical features in children (sensitivity 60.0% and specificity 61.2%) and a score of 5 in adults (sensitivity 54.6% and specificity 57.5%). The clinical features differed and algorithm performances were poorer than in previous studies in highly endemic areas. The conclusion is that malaria diagnosis in areas of low endemicity requires microscopy to be accurate. [ABSTRACT FROM AUTHOR]

To test the hypothesis that widespread treatment with artemisinin derivatives can reduce malaria transmission, a mass drug administration (MDA) campaign was undertaken in an area of The Gambia in 1999. Coverage of 85% of the target population was achieved, but the intervention did not reduce overall malaria transmission. We studied the perceptions, knowledge and attitudes of the community to the MDA campaign. A validated questionnaire was administered to randomly selected MDA participants (n = 90) and MDA refusers (n = 71). Individuals who believed in the importance of the MDA (adjusted OR 58.3%; 95% CI 17.4-195.8) and those who were aware that a high level of participation was needed for the MDA to be successful (adjusted OR 28.1; 95% CI 10.3-75.9) were more likely to participate. Understanding that the purpose of the MDA was to reduce malaria (adjusted OR 13.9; 95% CI 5.5-35.1) and knowledge of the fact that malaria is transmitted by mosquitoes and of the clinical signs of malaria (adjusted OR 3.4; 95% CI 3.1-9.0) were associated with participation. Individuals who discussed the MDA with other villagers (adjusted OR 5.5; 95% CI 2.2-13.5) and those who attended the sensitization meeting (adjusted OR 2.6; 95% CI 1.1-6.0) were also more likely to participate. Women were significantly more likely to participate in the MDA than men (adjusted OR 3.1; 95% CI 1.5-6.2). Individuals who refused to participate were unlikely to plan participation in future MDAs. One of the most difficult challenges in the implementation of a malaria control strategy such as an MDA is to convince villagers to participate and to make them aware that a high level of participation by the community is needed for success. We found that our sensitization meetings could be improved by giving more information on how the MDA works and finding means to generate small group discussions after the meeting. [ABSTRACT FROM AUTHOR]

There is evidence that season of birth may predict adult mortality from infectious diseases in rural Gambia. Using data collected over a five-year period from the rural, eastern region of the Gambia, we examined whether the season of birth influences mortality in childhood. 26 894 births and 3776 deaths among children under the age of five years were recorded in this region during the period 1989-1993. The estimated 1-4 year population was 95 355. In children aged 1-4 years, the mortality rate per 1000 per year was 16.1 (95% CI 14.9, 17.2) for those born in the 'harvest' season (January to June), which was not significantly different from the rate of 17.9 (95% CI 16.7, 19.0) recorded for those born in the 'hungry' season (July to December) (age-stratified Mantel-Haenszel mortality ratio 0. 91, 95% CI 0.83, 1.01; p = 0.08). Nearly all deaths of 1-4 year olds were attributed to infectious diseases, with malaria accounting for over 40%. None of the cause-specific child mortality rates differed significantly according to the season of birth. These data suggest that beyond infancy, when it is easier to separate the effect of season on cause of death from that of the season of birth, there is no marked difference in the rate of death between Gambian children born in the harvest season and those born in the hungry season. [ABSTRACT FROM AUTHOR]

Diagnosis of clinical malaria remains difficult, especially in areas where a high proportion of the asymptomatic population have parasitaemia, for the symptoms and signs of malaria overlap with those of other common childhood diseases, such as acute lower respiratory tract infections. However, a study of symptoms and signs in a group of children who presented to Farafenni Health Centre, The Gambia with a history of recent fever identified a group of signs and symptoms which were strong predictors of malaria as opposed to other febrile illnesses. Using these predictors, an algorithm was developed which could be used by fieldworkers and which had a similar sensitivity and specificity for the diagnosis of malaria as that of an experienced paediatrician working without laboratory support. This algorithm has been validated prospectively on 518 children who presented to the Medical Research Council clinic at Basse, The Gambia with fever or a history of recent fever during a 10-month period. A fieldworker obtained a detailed history from the parent or guardian of each child and performed a clinical examination which included measurement of axillary temperature and respiratory rate. Packed cell volume was measured and a thick smear was examined for malaria parasites. A malaria score, based on the presence or absence of malaria-related signs and symptoms, was determined for 382 children who were seen at the clinic during the high transmission season. Using the cut-off score which was optimal during the previous retrospective study, a sensitivity of 70% and a specificity of 77% for a diagnosis of malaria was obtained. The optimal cut-off score for the Basse population was a score of 7; this gave a sensitivity of 88% and a specificity of 62%, figures comparable to those obtained by an experienced paediatrician without laboratory support. [ABSTRACT FROM AUTHOR]

In developing countries, endemic childhood meningitis is a severe disease caused most commonly by Streptococcus pneumoniae or Haemophilus influenzae type b (Hib). Although many studies have shown that fatality rates associated with meningitis caused by these organisms are high in developing countries, little is known about the long-term outcome of survivors. The purpose of this study was to assess the importance of disabilities following pneumococcal and Hib meningitis in The Gambia. 257 children aged 0-12 years hospitalized between 1990 and 1995 with culture-proven S. pneumoniae (n = 134) or Hib (n = 123) meningitis were included retrospectively in the study. 48% of children with pneumococcal meningitis and 27% of children with Hib meningitis died whilst in hospital. Of the 160 survivors, 89 (55%) were followed up between September 1996 and October 1997. Of the children with pneumococcal meningitis that were traced, 58% had clinical sequelae; half of them had major disabilities preventing normal adaptation to social life. 38% of survivors of Hib meningitis had clinical sequelae, a quarter of whom had major disabilities. Major handicaps found were hearing loss, mental retardation, motor abnormalities and seizures. These data show that despite treatment with effective antibiotics, pneumococcal and Hib meningitis kill many Gambian children and leave many survivors with severe sequelae. Hib vaccination is now given routinely in The Gambia; an effective pneumococcal vaccine is needed. [ABSTRACT FROM AUTHOR]

Background: Acute lower respiratory tract infections (ALRI) are the major cause of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) infection is the most important viral cause of severe ALRI but only a small proportion of children infected with this virus develop severe disease. To identify possible risk factors for severe RSV infection leading to hospital admission we have carried out a case-control study of Gambian children with RSV infection admitted to hospital.Methods: In all, 277 children admitted to three hospitals in the Western Region of The Gambia with lower respiratory tract infection due to RSV were compared with 364 control children matched for age and location of residence who had not been admitted to hospital with an ALRI during the RSV season. A detailed questionnaire covering a wide range of potential social, environmental and nutritional risk factors was administered to the child's guardian.Results: Cases came from larger or more crowded compounds than controls; increased risk was particularly associated with greater numbers of children in the age group 3-5 years living in the compound (odds ratio [OR] for > or =2 children in the age group 3-5 years = 9.1, 95% CI: 3.7-28). Cases were more likely to have a sibling who had died (OR = 3.4, 95% CI: 1.7-7). Controls were more likely to have been exposed to smoke from cooking fires (OR for the mother of cases cooking at least once daily = 0.31, 95% CI: 0.14-0.7). Other protective factors were father's nationality and some professions. Vegetables were included in the diet of controls more frequently than in that of cases (OR = 0.16, 95% CI: 0.06-0.46). Mothers of cases complained of asthma more frequently than mothers of controls, but the number of asthmatic mothers was small (4.2 versus 0.5%, P = 0.05).Conclusions: Risk factors for severe RSV infection identified in this study are not amenable to public health interventions. Prevention of severe infection is likely to require the development of an effective vaccine. [ABSTRACT FROM AUTHOR]

Kidney function was studied in 80 Gambian children with cerebral malaria, 73 children with mild malaria, and in 19 children with other febrile illnesses. Serum creatinine was measured, and the excretion in urine of immunoglobulin G, transferrin, albumin and alpha 1 microglobulin was determined. Twenty-five percent of children with cerebral malaria, and 4% of children with mild malaria had an elevated serum creatinine above 62 mumol/l. Increased urinary protein excretion was frequent: 53% of children with cerebral malaria had a glomerulo-tubular pattern of protein excretion, and 46% a tubular pattern. Median albuminuria was 68 mg/l in children with cerebral malaria, 18 mg/l in children with mild malaria, and 9 mg/l in febrile children with other diseases (P < 0.0001). There was no significant association between the proteinuria and height of fever or the degree of parasitaemia, and there was no significant association between death and signs of renal impairment. Renal involvement is common in children with malaria in The Gambia, with prerenal, glomerular, and tubulo-interstitial factors contributing. It is more pronounced in children with cerebral malaria than in those with mild malaria. However, renal dysfunction is relatively mild and does not indicate a worse prognosis. [ABSTRACT FROM AUTHOR]