Brian Greenwood

..menafricar.org) and on the web site of the Centers for Disease Control (www.cdc.gov)...

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..In middle income countries, financial challenges predominate. These could be met by demonstration of the cost effectiveness of new meningococcal vaccines and through the introduction of a tiered-pricing system...

..A significant concern is whether IPTc increases children's susceptibility to subsequent malaria infection by altering their anti-Plasmodium acquired immunity...

..Therefore, entomological surveys were carried out in the forest-savannah transitional belt of Ghana (Kintampo) from November 2003 to November 2005 in preparation for drug and vaccine trials...

..This paper reviews published safety and efficacy data on various antimalarials and proposes several candidate combination regimens for assessment in phase II/III clinical trials...

..This might be achieved with some pre-erythrocytic stage candidate vaccines or by targeting the sexual stages directly with transmission-blocking vaccines. An expanded malaria vaccine programme with such objectives is now a priority...

..The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time...

..The present study was undertaken to investigate the clinical, parasitological and haematological status of adults exposed to malaria, and to characterize parasites in these individuals who progressively acquire protective immunity...

..Five of the six trials using sulphadoxine-pyrimethamine (SP) for IPTi showed protective efficacies (PEs) against clinical malaria ranging from 20.1 - 33.3% whilst one, the Ifakara study, showed a protective efficacy of 58.6%...

..As a background to the establishment of a site for anti-malarial drugs and vaccine trials, the epidemiology of malaria in a rural site in central Ghana was investigated...

..All-cause and malaria-specific mortality rates for children under-five years old in a mesoendemic malaria area (The Gambia) were compared with those from a hyper/holoendemic area (Burkina Faso)...

..The potential benefits of combining IPT in children (IPTc) with home management of malaria (HMM) was investigated...

..This study compares the molecular epidemiology of S. pneumoniae serotype 1 causing invasive disease in The Gambia between 1996 and 2005 to those carried in the nasopharynx between 2004 and 2006...

..The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children..

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..The potential benefits of intermittent preventive treatment in children are substantial; more research is needed to determine if this is a practical approach to malaria control...

..Capacity development, notably through a PhD programme, has been an underlying feature of all aspects of the programme...

..Other vaccines are being studied in clinical trials, but it will probably be at least 10 years before a malaria vaccine is ready for widespread use...

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..Novel approaches to surveillance will be necessary to ensure that once elimination has been achieved, it is not threatened by a rapid reintroduction of malaria from neighbouring areas...

..However, malaria elimination (cessation of local transmission) is a realistic short- to medium-term goal for an increasing number of countries that are already bringing malaria under control...

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..Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B...

..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...

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..Mass drug administration probably has little role to play in control of mortality and morbidity from malaria but may have an important role in the final stages of an elimination campaign...

..This review discusses how the use of molecular genetic techniques such as the polymerase chain reaction are helping in the management and prevention of malaria...

..Malaria vaccines with transmission-blocking properties could play a key role in future elimination programmes...

..Malaria vaccines will need to be more effective or more cost effective than these alternative control strategies or be able to provide substantial added value, when deployed with them if they are to be adopted widely...

..This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi...

..However, rising resistance to this combination is a concern. We investigated a shortacting and longacting antimalarial drug as alternative regimens for IPTi...

..We have evaluated the coverage of IPTc that can be achieved by two different delivery systems in Ghana...

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..Here we examine the relationship between the protective efficacy of SP-IPTi and measures of SP resistance...

..It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc...

..However, because of concerns about development of drug resistance, new combinations of long-acting drugs are urgently needed...

..However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy...

..To evaluate the effects of intermittent preventive treatment for malaria in infants (IPTi) with sulfadoxine-pyrimethamine in an area of intense, seasonal transmission...

..Health worker support for any MiP intervention delivered through ANC clinics is critical...

..Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp...

..This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time...

..We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection...

..To develop a decision-support tool to help policy-makers in sub-Saharan Africa assess whether intermittent preventive treatment in infants (IPTi) would be effective for local malaria control...

..A key challenge is the identification of a cost-effective delivery strategy...

..This paper reports on a complementary study investigating the acceptability of the different strategies to women enrolled in the trial...

..A greater understanding of the relationship between transmission intensity, seasonality and the age-pattern of malaria is needed to guide appropriate targeting of malaria interventions in different epidemiological settings...

..Whilst trials are underway to test the efficacy of future alternative approaches, it is important to start exploring the feasibility of their implementation...

..Generalisation of results over a wide geographic region, or between urban and rural settings, may not be appropriate...

..This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified...

..Progress towards GAVI's strategic aims is needed and funding is crucial. Approaches that decrease the financial pressure on GAVI and greatly increase political and financial engagement by low-income countries should also be considered...

..Experience with the development of Lapdap may provide a model for the introduction of other new drugs developed primarily for use in developing countries...

..There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs...

..But these new tools will achieve their maximum impact only if additional resources are deployed to strengthen malaria research and control communities in countries where the new tools will be used...

..The seroconversion rate (91%) based on a variable-fold increase in rSBA titre derived from the model was a more plausible estimate of immunogenicity than the seroconversion rate (32%) based on the fixed four-fold increase in rSBA...

..We have, therefore, undertaken a pooled analysis of existing data from multiple sites to enable a comprehensive overview of the age-patterns of malaria outcomes under different epidemiological conditions in sub-Saharan Africa...

..To determine the value of C-reactive protein (CRP) and procalcitonin in the evaluation of the efficacy of a pneumococcal conjugate vaccine in Gambian children...

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..Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST) at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women...

..We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens...

..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...

..One of the main challenges facing medical researchers in West Africa is how these new technologies can be used most effectively to improve health in countries with limited resources...

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..HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections...

..In highly endemic areas where laboratory support is not available, the policy of offering antimalarial drugs to all children presenting with a febrile illness recommended by the integrated child management initiative is appropriate...

..Thus, a strong case can be made for a trial of the effectiveness of maternal immunisation with a pneumococcal vaccine in preventing serious illness or death in young infants in developing countries...

..Causes assigned in this way have poor sensitivity and specificity. We illustrate the effects of this misclassification on the power of a large trial of a pneumococcal polysaccharide/protein conjugate vaccine with a mortality endpoint...

..However, no studies published to date have examined community perceptions of IPTc...

..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...

..The overall distribution of csp allelic variants was similar in infections occurring in vaccine and control groups. Also, the mean number of genotypes per infection in the RTS,S/AS02 group was not reduced compared with the controls...

..83 x 10(-4)), and were infective to Anopheles mosquitoes. Therapeutic success may thus be accompanied by public health failure as cured children pass resistance genes on to mosquitoes at an enhanced rate...

..These findings support the feasibility and potential of this approach to screen pre-erythrocytic vaccines for efficacy against infection in small numbers of vaccinees in endemic areas...

..To describe the epidemiology of respiratory syncytial virus (RSV) infection in a developing country...

..Being female, or febrile, or a referral and having low parasitaemia or hepatomegaly were the risk factors for severe anaemia...

..No significant association was found between severe malaria and either haptoglobin genotypes or phenotypes. The advantages of using a deoxyribonucleic acid-based haptoglobin typing method are discussed...

..The results are important for design of a vaccine to induce protective antibodies, and they address hypotheses about repeat sequences in malaria antigens...

..Importantly, this effect remained significant after adjusting for a simultaneous strong protective association of antibodies to another antigen (MSP1 block 2) which itself remained highly significant...

..These findings provide direct evidence for a protective role for CD4(+) T cells in humans, and a precise target for the design of improved vaccines against P. falciparum...

..It is also thought that an individual's ability to clear drug-resistant malarial parasites after treatment is enhanced by acquired immunity...

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..In this setting, ITC use was not associated with increased circulation of parasites resistant to standard antimalarial drugs, or with a greater risk of treatment failure among children less than 5 years of age...

..To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission...

..Sequence polymorphisms divide alleles into 2 major types, but the adaptive and immunological significance of the types has not been defined...

..However, this study has shown that in an area with a modest level of resistance to SP, use of a more effective antimalaria reduces the need for blood transfusion in children with malarial anaemia...

..To describe the characteristics of pneumococcal isolates obtained from patients with invasive pneumococcal disease in The Gambia...

..An understanding of the relationships among the level of exposure to Plasmodium falciparum, age, and severity of malaria can provide evidence of whether this is likely...

..The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation...

..A similar situation is likely in many other developing countries. Thus, equipment for measuring oxygen saturation, and facilities and equipment for effective oxygen delivery need to be made available in developing countries...

..6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission...

..The reason for the absence of an impact on malaria transmission is probably the very high basic reproductive number of malaria, and the persistence of mature gametocytes, which are not affected by AS treatment...

..This is the first evidence for an association between CD32 polymorphism and severe malaria and provides an example of balancing selective pressures from different infectious diseases operating at the same genetic locus...

..Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions...

..We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes...

..S. Dingiri, which possesses an antigenic formula of 17:z:1,6, was sensitive to ampicillin, cefotaxime, chloramphenicol, ciprofloxacin, cotrimoxazole and tetracycline but resistant to gentamicin, and was ST338...

..To prepare for national introduction of a pneumococcal conjugate vaccine of restricted valency, we studied nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants...