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Showing papers on "Malaria published in 2006"


Journal ArticleDOI
TL;DR: It is argued that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.
Abstract: Hotez et al. argue that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.

785 citations


Journal ArticleDOI
08 Dec 2006-Science
TL;DR: A mathematical model applied to a setting in Kenya with an adult population of roughly 200,000 estimated that, since 1980, the disease interaction may have been responsible for 8,500 excess HIV infections and 980,000 excess malaria episodes.
Abstract: Mounting evidence has revealed pathological interactions between HIV and malaria in dually infected patients, but the public health implications of the interplay have remained unclear. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes; in addition, susceptibility to malaria is enhanced in HIV-infected patients. A mathematical model applied to a setting in Kenya with an adult population of roughly 200,000 estimated that, since 1980, the disease interaction may have been responsible for 8,500 excess HIV infections and 980,000 excess malaria episodes. Co-infection might also have facilitated the geographic expansion of malaria in areas where HIV prevalence is high. Hence, transient and repeated increases in HIV viral load resulting from recurrent co-infection with malaria may be an important factor in promoting the spread of HIV in sub-Saharan Africa.

488 citations


Journal ArticleDOI
TL;DR: Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi.
Abstract: BACKGROUND In 1993, Malawi became the first country in Africa to replace chloroquine with the combination of sulfadoxine and pyrimethamine for the treatment of malaria. At that time, the clinical efficacy of chloroquine was less than 50%. The molecular marker of chloroquine-resistant falciparum malaria subsequently declined in prevalence and was undetectable by 2001, suggesting that chloroquine might once again be effective in Malawi. METHODS We conducted a randomized clinical trial involving 210 children with uncomplicated Plasmodium falciparum malaria in Blantyre, Malawi. The children were treated with either chloroquine or sulfadoxine–pyrimethamine and followed for 28 days to assess the antimalarial efficacy of the drug. RESULTS In analyses conducted according to the study protocol, treatment failure occurred in 1 of 80 participants assigned to chloroquine, as compared with 71 of 87 participants assigned to sulfadoxine–pyrimethamine. The cumulative efficacy of chloroquine was 99% (95% confidence interval [CI], 93 to 100), and the efficacy of sulfadoxine–pyrimethamine was 21% (95% CI, 13 to 30). Among children treated with chloroquine, the mean time to parasite clearance was 2.6 days (95% CI, 2.5 to 2.8) and the mean time to the resolution of fever was 10.3 hours (95% CI, 8.1 to 12.6). No unexpected adverse events related to the study drugs occurred. CONCLUSIONS Chloroquine is again an efficacious treatment for malaria, 12 years after it was withdrawn from use in Malawi. (ClinicalTrials.gov number, NCT00125489.)

415 citations


Journal ArticleDOI
TL;DR: The importance of pfmdr1 copy number in determining P. falciparum susceptibility to multiple agents currently being used to combat malaria caused by multidrug-resistant parasites is highlighted.
Abstract: The global dissemination of drug-resistant Plasmodium falciparum is spurring intense efforts to implement artemisinin (ART)-based combination therapies for malaria, including mefloquine (MFQ)-artesunate and lumefantrine (LUM)-artemether. Clinical studies have identified an association between an increased risk of MFQ, MFQ-artesunate, and LUM-artemether treatment failures and pfmdr1 gene amplification. To directly address the contribution that pfmdr1 copy number makes to drug resistance, we genetically disrupted 1 of the 2 pfmdr1 copies in the drug-resistant FCB line, which resulted in reduced pfmdr1 mRNA and protein expression. These knockdown clones manifested a 3-fold decrease in MFQ IC(50) values, compared with that for the FCB line, verifying the role played by pfmdr1 expression levels in mediating resistance to MFQ. These clones also showed increased susceptibility to LUM, halofantrine, quinine, and ART. No change was observed for chloroquine. These results highlight the importance of pfmdr1 copy number in determining P. falciparum susceptibility to multiple agents currently being used to combat malaria caused by multidrug-resistant parasites.

391 citations


Journal ArticleDOI
TL;DR: TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation are suggested, however some gray areas also suggest the scope for further improvements.
Abstract: Genetic host factors play a substantial role in susceptibility to and severity of malaria, which continues to cause at least one million deaths per year. Recently, members of the toll-like receptor (TLR) family have been shown to be involved in recognition of the etiologic organism Plasmodium falciparum: The glycosylphosphatidylinositol anchor induces signaling in host cells via TLR-2 and -4, whereas hemozoin-induced immune activation involves TLR-9. Binding of microbial ligands to the respective TLRs triggers the release of proinflammatory cytokines via the TLR/IL-1 receptor (TIR) domain and may contribute to the host response in malaria, including cytokine induction and fever. In a case-control study among 870 Ghanaian children, we examined the influence of TLR-2, -4, and -9 polymorphisms in susceptibility to severe malaria. TLR-2 variants common in Caucasians and Asians were completely absent. However, we found a rare previously undescribed mutation (Leu658Pro), which impairs signaling via TLR-2. We failed to detect any polymorphisms within the TLR-9 Toll/IL-1 receptor domain. Two frequent TLR-9 promoter polymorphisms did not show a clear association with malaria severity. In contrast, the TLR-4-Asp299Gly variant occurred at a high rate of 17.6% in healthy controls and was even more frequent in severe malaria patients (24.1%, P < 0.05). Likewise, TLR-4-Thr399Ile was seen in 2.4% of healthy children and in 6.2% of patients (P = 0.02). TLR-4-Asp299Gly and TLR-4-Thr399Ile conferred 1.5- and 2.6-fold increased risks of severe malaria, respectively. These findings suggest TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation.

347 citations


Journal ArticleDOI
TL;DR: There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovale malaria; presumptive anti-relapse therapy (PART) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species.
Abstract: Primaquine phosphate has been used for preventing relapse of Plasmodium vivax and P. ovale malaria since the early 1950s, based on its ability to kill latent (hypnozoite) and developing liver stages of these parasites. There are three uses for primaquine in malaria: radical cure of established infection with P. vivax or P. ovale malaria; presumptive anti-relapse therapy (PART; terminal prophylaxis) in persons with extensive exposure to these parasites; and primary prophylaxis against all malaria species. All persons for whom primaquine is being considered must have a glucose-6-phosphate dehydrogenase (G6PD) enzyme level checked before use, and persons who have a deficiency of G6PD must not take primaquine for prophylaxis or PART. The recommended adult dose for PART based on clinical trials and expert opinion is 30 mg base daily for 14 days, started on return from a malarious region and overlapping with a blood schizonticide. The adult dose for primary prophylaxis is 30 mg daily begun 1 day before travel and continued for 7 days after return. This review will examine the evidence for these recommendations.

330 citations


Journal ArticleDOI
TL;DR: Current knowledge of malarial retinopathy is reviewed, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria are reviewed.
Abstract: Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.

323 citations


Journal ArticleDOI
TL;DR: These estimates, based on the best available data and methods, clearly demonstrate malaria's enormous mortality burden and emphasize that these estimates are an approximation with many limitations and that the estimates do not account for malaria's large indirect burden.
Abstract: Results The literature review identified 31 studies from 14 countries in middle Africa and 17 studies and reports from four countries in southern Africa. In 2000, we estimated that ~100 million children lived in areas where malaria transmission occurs and that 803 620 (precision estimate: 705 821–901 418) children died from the direct effects of malaria. For all of sub-Saharan Africa, including populations not exposed to malaria, malaria accounted for 18.0% (precision estimate: 15.8–20.2%) of child deaths. These estimates were sensitive to extreme assumptions about the causes of deaths with no known cause. Conclusions These estimates, based on the best available data and methods, clearly demonstrate malaria’s enormous mortality burden. We emphasize that these estimates are an approximation with many limitations and that the estimates do not account for malaria’s large indirect burden. We describe information needs that, if filled, might improve the validity of future estimates.

310 citations


Journal ArticleDOI
TL;DR: The lumefantrine plasma concentration profile is the main determinant of efficacy of artemether-lumefanrine in patients with uncomplicated Plasmodium falciparum malaria and, therefore, treatment responses when plasma lumfantrine levels are subtherapeutic.
Abstract: The emergence of drug resistance in Plasmodium falciparum has significantly undermined malaria-control programs in countries where it is endemic [1]. To ensure high cure rates and to combat this threat, the World Health Organization (WHO) has recommended the use of artemisinin combination therapy (ACT), although debate regarding the most suitable combination and how ACTs should be deployed and funded still continues. Artemisinins ensure rapid reduction of the initial infecting biomass, with the residual parasites being removed by a more slowly eliminated component usually included in combination therapy. The rationale supporting the use of ACT is improvement of anti-malarial efficacy, facilitation of adherence to a full treatment course, and minimization of selection of drug-resistant parasites. Artemether-lumefantrine (AL) is currently the only combination therapy widely available that is manufactured to Good Manufacturing Practice standards in a fixed-dose preparation (each tablet contains 20 mg of artemether and 120 mg of lumefantrine). The fixed-dose regimen ensures that malaria parasites always encounter artemether and metabolites in the presence of lumefantrine and provides protection against the emergence of resistance to both components, but absorption of the lipophilic lumefantrine is erratic, and the drug needs to be administered twice per day [2]. Therapeutic levels are more reliably achieved by coadministration with a fatty meal and by extending the treatment course from 4 to 6 doses [3-5]. The WHO now advocates the higher, 6-dose regimen for the treatment of P. falciparum malaria in all areas, irrespective of the levels of host immunity or prevalence of multidrug resistance. On the western border of Thailand, P. falciparum has become resistant to chloroquine, sulfadoxine-pyrimethamine, mefloquine, and halofantrine [6], although there have been no convincing reports of clinical resistance to the artemisinin derivatives. In studies conducted to determine the molecular basis of mefloquine resistance, we have highlighted a central role of amplification of pfmdr1 [7]. In vitro cross-resistance has been observed between lumefantrine, mefloquine, and halofantrine, and subsequent molecular studies have suggested a common mechanism of resistance [8]. We hypothesized that pfmdr1 polymorphisms would also contribute to treatment failure following AL treatment. To investigate the relative contributions of host, pharmacokinetic, and parasitological factors in determining therapeutic outcome following treatment with AL, we analyzed the cumulative AL experience at the Shoklo Malaria Research Unit (SMRU; Mae Sod, Tak Province, Thailand) between 1995 and 2002.

303 citations


Journal ArticleDOI
TL;DR: The primary goal of the recently launched Malaria Atlas Project is to develop the science of malaria cartography.
Abstract: The primary goal of the recently launched Malaria Atlas Project is to develop the science of malaria cartography.

299 citations


Journal ArticleDOI
TL;DR: A de-trended time series of temperature was used and a warming trend in the East African highlands from 1950 to 2002 was documented, concomitant with increases in malaria incidence, confirming the importance of the well recognized nonlinear and threshold responses of malaria (a biological system) to the effect of regional temperature change.
Abstract: An estimated 700,000 to 2.7 million people die of malaria each year, and 75% of those are African children (www.cdc.gov/malaria). Recent resurgence in the East African highlands involves multiple factors, from climate and land use change to drug resistance, variable disease control efforts, and other sociodemographic factors (1). But malaria is an extremely climate-sensitive tropical disease, making the assessment of potential change in risk due to past and projected warming trends one of the most important climate change/health questions to resolve. Pascual et al . (2) now provide important new insights toward answering this malaria/climate question in their article in this issue of PNAS. Pascual’s research team used a de-trended time series of temperature and documented a warming trend in the East African highlands from 1950 to 2002, concomitant with increases in malaria incidence. Moreover, their findings confirm the importance of the well recognized nonlinear and threshold responses of malaria (a biological system) to the effect of regional temperature change (Fig. 1). For example, showing that the biological response of mosquito populations to warming can be more than an order of magnitude larger than the measured change in temperature represents a stunning finding, critical in advancing risk assessment of climate change impacts. Those who argue that we need not worry about small shifts in temperature should … *To whom correspondence should be addressed. E-mail: patz{at}wisc.edu

Journal ArticleDOI
TL;DR: Guidelines for travellers on malaria chemoprophylaxis, the altitude limits of dominant vector species, climate suitability for malaria transmission and human population density thresholds have been used to map the crude spatial limits of Plasmodium falciparum and Plas modal transmission on a global scale.

Journal ArticleDOI
TL;DR: Based on the observed behavior of the vectors, insecticide-treated bed nets will be highly effective in controlling malaria, however, in the high transmission areas, additional measures will be needed to reduce the malaria burden to acceptable levels.
Abstract: Knowledge of the baseline malaria transmission in a given environment is important to guide malaria control interventions. However, in Uganda, recent information on malaria transmission intensity is lacking. Therefore, a 1-year entomological study was conducted in seven ecologically different sites throughout the country to assess spatial and temporal patterns in malaria transmission intensity. Anopheles gambiae sensu stricto was the main vector in five of the seven study sites, and An. funestus was the most important vector in the two other sites. In a peri-urban village, An. arabiensis contributed substantially to malaria transmission. Clear differences in annual entomological inoculation rates (AEIR) were observed between the study sites, ranging from 4 infective bites per person per year in the southwestern part of the country to >1,500 infective bites per person per year in a swampy area near the Nile River. Between villages with parasite prevalences of >or= 80% in children between 1 and 9 years old, a 4-fold difference in AEIR was observed. Based on the observed behavior of the vectors, insecticide-treated bed nets will be highly effective in controlling malaria. However, in the high transmission areas, additional measures will be needed to reduce the malaria burden to acceptable levels.

Journal ArticleDOI
28 Apr 2006-Science
TL;DR: Survey of an Anopheles gambiae population in a West African malaria transmission zone for naturally occurring genetic loci that control mosquito infection with the human malaria parasite finds the strongest Plasmodium resistance loci cluster in a small region of chromosome 2L and each locus explains at least 89% of parasite-free mosquitoes in independent pedigrees.
Abstract: We surveyed an Anopheles gambiae population in a West African malaria transmission zone for naturally occurring genetic loci that control mosquito infection with the human malaria parasite, Plasmodium falciparum. The strongest Plasmodium resistance loci cluster in a small region of chromosome 2L and each locus explains at least 89% of parasite-free mosquitoes in independent pedigrees. Together, the clustered loci form a genomic Plasmodium-resistance island that explains most of the genetic variation for malaria parasite infection of mosquitoes in nature. Among the candidate genes in this chromosome region, RNA interference knockdown assays confirm a role in Plasmodium resistance for Anopheles Plasmodium-responsive leucine-rich repeat 1 (APL1), encoding a leucine-rich repeat protein that is similar to molecules involved in natural pathogen resistance mechanisms in plants and mammals.

Journal ArticleDOI
TL;DR: Eritrea has within 5 years attained key Roll Back Malaria targets and the effects and possible interactions between the public health interventions in use contributed most to reducing malaria morbidity.
Abstract: Malaria is a huge public health problem in Africa that is responsible for more than one million deaths annually. In line with the Roll Back Malaria initiative and the Abuja Declaration, Eritrea and other African countries have intensified their fight against malaria. This study examines the impact of Eritrea's Roll Back Malaria Programme: 2000–2004 and the effects and possible interactions between the public health interventions in use. This study employed cross-sectional survey to collect data from households, community and health facilities on coverage and usage of Insecticide-Treated Nets (ITNs), Indoor Residual Spraying (IRS), larvicidal activities and malaria case management. Comparative data was obtained from a similar survey carried out in 2001. Data from the Health Management Information System (HMIS) and reports of the annual assessments by the National Malaria Control Programme was used to assess impact. Time series model (ARIMA) was used to assess association. In the period 2000–2004, approximately 874,000 ITNs were distributed and 13,109 health workers and community health agents were trained on malaria case management. In 2004, approximately 81% households owned at least one net, of which 73% were ITNs and 58.6% of children 0–5 years slept under a net. The proportion of malaria cases managed by community health agents rose from 50% in 1999 to 78% in 2004. IRS coverage increased with the combined amount of DDT and Malathion used rising from 6,444 kg, in 2000 to 43,491 kg, in 2004, increasing the population protected from 117,017 to 259,420. Drug resistance necessitated regimen change to chloroquine plus sulfadoxine-pyrimethamine. During the period, there was a steep decline in malaria morbidity and case fatality by 84% and 40% respectively. Malaria morbidity was strongly correlated to the numbers of ITNs distributed (β = -0.125, p < 0.005) and the amount (kg) of DDT and Malathion used for IRS (β = -2.352, p < 0.05). The correlation between malaria case fatality and ITNs, IRS, population protected and annual rainfall was not statistically significant. Eritrea has within 5 years attained key Roll Back Malaria targets. ITNs and IRS contributed most to reducing malaria morbidity.

Journal ArticleDOI
TL;DR: Evidence for mechanisms that influence the blood-brain barrier during malaria are summarised, including metabolic and inflammatory complications of severe disease acting 'at a distance' and the possible role for BBB dysfunction in this complex and challenging disease.

Journal ArticleDOI
TL;DR: This is believed to be the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.
Abstract: Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.

Journal ArticleDOI
TL;DR: It is shown that specific Mhc variants are linked to both increased resistance and susceptibility to malaria infection in a wild passerine species, the house sparrow (Passer domesticus), the first evidence for a population‐specific genetic control of resistance to malaria in aWild species.
Abstract: Malaria parasites are a major cause of human mortality in tropical countries and a potential threat for wildlife, as witnessed by the malaria-induced extinction of naive Hawaiian avifauna. Identifying resistance mechanisms is therefore crucial both for human health and wildlife conservation. Patterns of malaria resistance are known to be highly polygenic in both humans and mice, with marked contributions attributed to major histocompatibility (Mhc) genes. Here we show that specific Mhc variants are linked to both increased resistance and susceptibility to malaria infection in a wild passerine species, the house sparrow (Passer domesticus). In addition, links between host immunogenetics and resistance to malaria involved population-specific alleles, suggesting local adaptation in this host-parasite interaction. This is the first evidence for a population-specific genetic control of resistance to malaria in a wild species.

Journal ArticleDOI
TL;DR: A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Journal ArticleDOI
TL;DR: Studies on co‐infections in both animal models and in human populations and the implications of helminth infection for the efficacy of malaria vaccines will be discussed.
Abstract: SUMMARY Chronic helminth infections induce strong type 2 and regulatory immune responses and are known to influence immune activity to other antigens such as allergens and vaccines. Since malaria and helminth infections often coincide geographically in the same tropical regions, the question arises whether helminth infections modulate the immune responses towards the malaria parasite and affect its course of disease. Here, we will review studies on co-infections in both animal models and in human populations, and discuss the changes in the immune system seen. Furthermore, the implications of helminth infection for the efficacy of malaria vaccines will be discussed.

Journal ArticleDOI
TL;DR: The mechanisms by which anti‐malarial immune responses are believed to be regulated were discussed at the recent Malaria Immunology Workshop and potential regulatory mechanisms include regulatory T cells, which have been shown to significantly modify cellular immune responses to various protozoan infections.
Abstract: The optimal outcome of a malaria infection is that parasitized cells are killed and degraded without inducing significant pathology. Since much of the pathology of malaria infection can be immune-mediated, this implies that immune responses have to be carefully regulated. The mechanisms by which anti-malarial immune responses are believed to be regulated were discussed at the recent Malaria Immunology Workshop (Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; February 2005). Potential regulatory mechanisms include regulatory T cells, which have been shown to significantly modify cellular immune responses to various protozoan infections, including leishmania and malaria; neutralising antibodies to pro-inflammatory malarial toxins such as glycosylphosphatidylinositol and haemozoin; and self-regulating networks of effector molecules. Innate and adaptive immune responses are further moderated by the broader immunological environment, which is influenced by both the genetic background of the host and by co-infection with other pathogens. A detailed understanding of the interplay between these different immunoregulatory processes may facilitate the rationale design of vaccines and novel therapeutics.

Journal ArticleDOI
TL;DR: Data on gametocyte carriage is reviewed in the context of the development of naturally acquired immunity and population infectivity in Sub-Saharan Africa.

Journal ArticleDOI
TL;DR: Clinical diagnosis of invasive nontyphoidal Salmonella infection in African children is difficult without microbiology facilities because clinical features overlap with other conditions.
Abstract: Nontyphoidal Salmonella spp. are among the leading causes of childhood bacteremia in sub-Saharan Africa yet there are few published clinical series and the risk factors for acquiring infection are not fully understood. We examined data from 166 cases of nontyphoidal Salmonella bacteremia identified during a large prospective study of bacteremia among all children admitted to a district hospital in Kenya. We also investigated the importance of comorbidities including current malaria parasitemia recent malaria (detectable Plasmodium falciparum histidine rich protein 2 in the absence of parasitemia) sickle cell disease malnutrition and human immunodeficiency virus (HIV) infection. Nontyphoidal Salmonella bacteremia was associated with severe malnutrition (33% cases) HIV infection (18% cases) a history of illness > 7 days recent hospital admission splenomegaly anemia and recent (but not current) malaria but was not associated with diarrhea. Seventy-seven (46%) children with nontyphoidal Salmonella bacteremia fulfilled World Health Organization clinical criteria for a diagnosis of pneumonia. Independent risk factors for death were diarrhea tachypnea HIV infection severe malnutrition meningitis and young age. Clinical diagnosis of invasive nontyphoidal Salmonella infection in African children is difficult without microbiology facilities because clinical features overlap with other conditions. The common risk factors for nontyphoidal Salmonella infection differ from developed countries with high a prevalence of malnutrition HIV malaria and anemia. Children with nontyphoidal Salmonella infection who fulfill World Health Organization clinical criteria for severe pneumonia may receive ineffective therapy in the form of penicillin. (authors)


Journal ArticleDOI
TL;DR: It is suggested that var genes with DBLα1-like domains (Group A or B/A) may be implicated in the pathogenesis of cerebral malaria, while var genes in other groups promote less virulent malaria infections.

Journal ArticleDOI
TL;DR: Genetic factors are a major determinant of child survival in malaria endemic countries and identifying which genes are involved and how they affect the malaria disease risk potentially offers a powerful mechanism through which to learn more about the host-parasite relationship.

Journal ArticleDOI
TL;DR: Malnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia, even if the latter exhibits multifactorial patterns, and the data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs.
Abstract: Malaria anemia and malnutrition contribute substantially to childhood morbidity in sub-Saharan Africa but their respective roles and interactions in conferring disease are complex. We aimed to investigate these interactions. In 2002 we assessed plasmodial infection anemia and nutritional indices in 2 representative surveys comprising > 4000 children in northern Ghana. Infection with Plasmodium species was observed in 82% and 75% of children in the rainy and dry season respectively. The fraction of fever attributable to malaria was 77% in the rainy season and 48% in the dry season and peaked in children of rural residence. Anemia (hemoglobin level < 11 g/dL) was seen in 64% of children and was in multivariate analysis associated with young age season residence parasitemia P. malariae coinfection and malnutrition (odds ratio [OR] 1.68 [95% confidence interval {CI} 1.38--2.04]). In addition malnutrition was independently associated with fever (axillary temperature = 37.5°C; OR 1.59 [95% CI 1.13--2.23]) and clinical malaria (OR 1.67 [95% CI 1.10--2.50]). Malnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia even if the latter exhibits multifactorial patterns. Our data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs. (authors)

Journal ArticleDOI
TL;DR: A major project to develop integrated mathematical models for predicting the epidemiologic and economic effects of malaria vaccines both at the individual and population level, allowing for the temporal dynamics of effects on immunity and transmission.
Abstract: We report a major project to develop integrated mathematical models for predicting the epidemiologic and economic effects of malaria vaccines both at the individual and population level. The project has developed models of the within-host dynamics of Plasmodium falciparum that have been fitted to parasite density profiles from malaria therapy patients, and simulations of P. falciparum epidemiology fitted to field malariologic datasets from a large ensemble of settings across Africa. The models provide a unique platform for predicting both the short- and long-term effects of malaria vaccines on the burden of disease, allowing for the temporal dynamics of effects on immunity and transmission. We discuss how the models can be used to obtain robust cost-effectiveness estimates for a wide range of malaria vaccines and vaccination delivery strategies in different eco-epidemiologic settings. This paper outlines for a non-mathematical audience the approach we have taken and its underlying rationale.

Journal ArticleDOI
TL;DR: The results suggest that the control of parasitic helminths and of malaria in school children could be viewed as essential co-contributors to promoting the health of schoolchildren.
Abstract: Surprisingly little is known about the geographical overlap between malaria and other tropical diseases, including helminth infections. This is despite the potential public health importance of co-infection and synergistic opportunities for control. Statistical models are presented that predict the large-scale distribution of hookworm in sub-Saharan Africa (SSA), based on the relationship between prevalence of infection among schoolchildren and remotely sensed environmental variables. Using a climate-based spatial model of the transmission potential for Plasmodium falciparum malaria, adjusted for urbanization, the spatial congruence of populations at coincident risk of infection is determined. The model of hookworm indicates that the infection is widespread throughout Africa and that, of the 179.3 million school-aged children who live on the continent, 50.0 (95% CI: 48.9–51.1) million (27.9% of total population) are infected with hookworm and 45.1 (95% CI: 43.9–46) million are estimated to be at risk of coincident infection. Malaria and hookworm infection are widespread throughout SSA and over a quarter of school-aged children in sub-Saharan Africa appear to be at risk of coincident infection and thus at enhanced risk of clinical disease. The results suggest that the control of parasitic helminths and of malaria in school children could be viewed as essential co-contributors to promoting the health of schoolchildren.

Reference EntryDOI
TL;DR: Chemoprophylaxis or IPT reduces antenatal parasite prevalence and placental malaria when given to women in all parity groups and has positive effects on birthweight and possibly on perinatal death in low-parity women.
Abstract: Background Malaria contributes to maternal illness and anaemia in pregnancy, especially in first-time mothers, and can harm the mother and the baby. Drugs given routinely to prevent or mitigate the effects of malaria during pregnancy are often recommended. Objectives To assess drugs given to prevent malaria infection and its consequences in pregnant women living in malarial areas. This includes prophylaxis and intermittent preventive treatment (IPT). Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register ( March 2006), CENTRAL ( The Cochrane Library 2006, Issue 1), MEDLINE ( 1966 to March 2006), EMBASE ( 1974 to March 2006), LILACS ( 1982 to March 2006), and reference lists. We also contacted researchers working in the field. Selection criteria Randomized and quasi-randomized controlled trials comparing antimalarial drugs given regularly with no antimalarial drugs for preventing malaria in pregnant women living in malaria-endemic areas. Data collection and analysis Both authors extracted data and assessed methodological quality. Dichotomous variables were combined using relative risks (RR) and weighted mean differences (WMD) for mean values, both with 95% confidence intervals (CI). Main results Sixteen trials ( 12,638 participants) met the inclusion criteria; two used adequate methods to conceal allocation. Antimalarials reduced antenatal parasitaemia when given to all pregnant women (RR 0.53, 95% CI 0.33 to 0.86; 328 participants, 2 trials), placental malaria ( RR 0.34, 95% CI 0.26 to 0.45; 1236 participants, 3 trials), but no effect was detected with perinatal deaths ( 2890 participants, 4 trials). In women in their first or second pregnancy, antimalarial drugs reduced severe antenatal anaemia (RR 0.62, 95% CI 0.50 to 0.78; 2809 participants, 1 prophylaxis and 2 IPT trials), antenatal parasitaemia (RR 0.27, 95% CI 0.17 to 0.44, random-effects model; 2906 participants, 6 trials), and perinatal deaths ( RR 0.73, 95% CI 0.53 to 0.99; 1986 participants, 2 prophylaxis and 1 IPT trial; mean birthweight was higher ( WMD 126.70 g, 95% CI 88.64 to 164.75 g; 2648 participants, 8 trials), and low birthweight less frequent ( RR 0.57, 95% CI 0.46 to 0.72; 2350 participants, 6 trials). Proguanil performed better than chloroquine in one trial of women of all parities in relation to maternal fever episodes. Sulfadoxine-pyrimethamine performed better than chloroquine in two trials of low-parity women. Authors' conclusions Chemoprophylaxis or IPT reduces antenatal parasite prevalence and placental malaria when given to women in all parity groups. They also have positive effects on birthweight and possibly on perinatal death in low-parity women.