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Showing papers on "Malaria published in 2007"


Journal ArticleDOI
TL;DR: In this article, the authors reviewed evidence of the clinical implications and burden of malaria in pregnancy and found that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae.
Abstract: We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100 000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.

988 citations


Journal ArticleDOI
TL;DR: This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials.
Abstract: The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.

858 citations


Journal ArticleDOI
TL;DR: Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria.
Abstract: Plasmodium vivax threatens almost 40% of the world's population, resulting in 132-391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite's ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.

801 citations


Journal ArticleDOI
TL;DR: Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years and indicated that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.
Abstract: BACKGROUND The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ("under five") and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar. METHODS AND FINDINGS Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period. CONCLUSIONS Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

621 citations


Journal ArticleDOI
TL;DR: Understanding of placental immunopathology and how this contributes to anaemia and low birthweight remains restricted, although inflammatory cytokines produced by T cells, macrophages, and other cells are clearly important.
Abstract: Understanding of the biological basis for susceptibility to malaria in pregnancy was recently advanced by the discovery that erythrocytes infected with Plasmodium falciparum accumulate in the placenta through adhesion to molecules such as chondroitin sulphate A. Antibody recognition of placental infected erythrocytes is dependent on sex and gravidity, and could protect from malaria complications. Moreover, a conserved parasite gene-var2csa-has been associated with placental malaria, suggesting that its product might be an appropriate vaccine candidate. By contrast, our understanding of placental immunopathology and how this contributes to anaemia and low birthweight remains restricted, although inflammatory cytokines produced by T cells, macrophages, and other cells are clearly important. Studies that unravel the role of host response to malaria in pathology and protection in the placenta, and that dissect the relation between timing of infection and outcome, could allow improved targeting of preventive treatments and development of a vaccine for use in pregnant women.

548 citations


Journal ArticleDOI
TL;DR: A community randomized, controlled trial of permethrin treated bednets among a rural population on the Kenyan Coast assessed the impact of ITBN on child survival under different epidemiological and cultural conditions.
Abstract: New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7-51%) and severe, life-threatening malaria among children aged 1-59 months (PE 44%, CI 19-62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.

484 citations


Journal ArticleDOI
22 Feb 2007-BMJ
TL;DR: Use of rapid diagnostic tests for malaria with routine microscopy, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria.
Abstract: Objective To compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients. Design Randomised trial. Setting Outpatient departments in northeast Tanzania at varying levels of malaria transmission. Participants 2416 patients for whom a malaria test was requested. Intervention Staff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopy Main outcome measure Proportion of patients with a negative test prescribed an antimalarial drug. Results Of 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P Conclusions Although many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians9 management of febrile illness are essential but will not be easy. Trial registration Clinical trials NCT00146796.

456 citations


Journal ArticleDOI
TL;DR: In India, nine Anopheline vectors are involved in transmitting malaria in diverse geo-ecological paradigms and about 2 million confirmed malaria cases and 1,000 deaths are reported annually, although 15 million cases and 20, 000 deaths are estimated by WHO South East Asia Regional Office as mentioned in this paper.
Abstract: In India, nine Anopheline vectors are involved in transmitting malaria in diverse geo-ecological paradigms. About 2 million confirmed malaria cases and 1,000 deaths are reported annually, although 15 million cases and 20,000 deaths are estimated by WHO South East Asia Regional Office. India contributes 77% of the total malaria in Southeast Asia. Multi-organ involvement/dysfunction is reported in both Plasmodium falciparum and P. vivax cases. Most of the malaria burden is borne by economically productive ages. The states inhabited by ethnic tribes are entrenched with stable malaria, particularly P. falciparum with growing drug resistance. The profound impact of complicated malaria in pregnancy includes anemia, abortions, low birth weight in neonates, still births, and maternal mortality. Retrospective analysis of burden of malaria showed that disability adjusted life years lost due to malaria were 1.86 million years. Cost-benefit analysis suggests that each Rupee invested by the National Malaria Control Program pays a rich dividend of 19.7 Rupees.

422 citations


Journal ArticleDOI
TL;DR: This work estimates R 0 in a novel way for 121 African populations, and thereby increases the number of R 0 estimates for malaria by an order of magnitude, which strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum.
Abstract: The prospects for the success of malaria control depend, in part, on the basic reproductive number for malaria, R0. Here, we estimate R0 in a novel way for 121 African populations, and thereby increase the number of R0 estimates for malaria by an order of magnitude. The estimates range from around one to more than 3,000. We also consider malaria transmission and control in finite human populations, of size H. We show that classic formulas approximate the expected number of mosquitoes that could trace infection back to one mosquito after one parasite generation, Z0(H), but they overestimate the expected number of infected humans per infected human, R0(H). Heterogeneous biting increases R0 and, as we show, Z0(H), but we also show that it sometimes reduces R0(H); those who are bitten most both infect many vectors and absorb infectious bites. The large range of R0 estimates strongly supports the long-held notion that malaria control presents variable challenges across its transmission spectrum. In populations where R0 is highest, malaria control will require multiple, integrated methods that target those who are bitten most. Therefore, strategic planning for malaria control should consider R0, the spatial scale of transmission, human population density, and heterogeneous biting.

421 citations


Journal ArticleDOI
TL;DR: Covering entire populations will be required to accomplish large reductions of the malaria burden in Africa, and coverage of vulnerable groups should still be prioritized, but the equitable and communal benefits of wide-scale ITN use by older children and adults should be explicitly promoted and evaluated by national malaria control programmes.
Abstract: Background Malaria prevention in Africa merits particular attention as the world strives toward a better life for the poorest. Insecticide-treated nets (ITNs) represent a practical means to prevent malaria in Africa, so scaling up coverage to at least 80% of young children and pregnant women by 2010 is integral to the Millennium Development Goals (MDG). Targeting individual protection to vulnerable groups is an accepted priority, but community-level impacts of broader population coverage are largely ignored even though they may be just as important. We therefore estimated coverage thresholds for entire populations at which individual- and community-level protection are equivalent, representing rational targets for ITN coverage beyond vulnerable groups. Methods and Findings Using field-parameterized malaria transmission models, we show that high (80% use) but exclusively targeted coverage of young children and pregnant women (representing <20% of the population) will deliver limited protection and equity for these vulnerable groups. In contrast, relatively modest coverage (35%–65% use, with this threshold depending on ecological scenario and net quality) of all adults and children, rather than just vulnerable groups, can achieve equitable community-wide benefits equivalent to or greater than personal protection. Conclusions Coverage of entire populations will be required to accomplish large reductions of the malaria burden in Africa. While coverage of vulnerable groups should still be prioritized, the equitable and communal benefits of wide-scale ITN use by older children and adults should be explicitly promoted and evaluated by national malaria control programmes. ITN use by the majority of entire populations could protect all children in such communities, even those not actually covered by achieving existing personal protection targets of the MDG, Roll Back Malaria Partnership, or the US President's Malaria Initiative.

365 citations


Journal ArticleDOI
TL;DR: Preventing and promptly treating malaria, providing appropriate vaccines, and identifying ways to reach travelers whose purpose for travel is visiting friends and relatives in advance of travel can reduce the burden of travel-related illness.
Abstract: Background Fever is a marker of potentially serious illness in returned travelers. Information about causes of fever, organized by geographic area and traveler characteristics, can facilitate timely, appropriate treatment and preventive measures. Methods Using a large, multicenter database, we assessed how frequently fever is cited as a chief reason for seeking medical care among ill returned travelers. We defined the causes of fever by place of exposure and traveler characteristics. Results Of 24,920 returned travelers seen at a GeoSentinel clinic from March 1997 through March 2006, 6957 (28%) cited fever as a chief reason for seeking care. Of patients with fever, 26% were hospitalized (compared with 3% who did not have fever); 35% had a febrile systemic illness, 15% had a febrile diarrheal disease, and 14% had fever and a respiratory illness. Malaria was the most common specific etiologic diagnosis, found in 21% of ill returned travelers with fever. Causes of fever varied by region visited and by time of presentation after travel. Ill travelers who returned from sub-Saharan Africa, south-central Asia, and Latin America whose reason for travel was visiting friends and relatives were more likely to experience fever than any other group. More than 17% of travelers with fever had a vaccine-preventable infection or falciparum malaria, which is preventable with chemoprophylaxis. Malaria accounted for 33% of the 12 deaths among febrile travelers. Conclusions Fever is common in ill returned travelers and often results in hospitalization. The time of presentation after travel provides important clues toward establishing a diagnosis. Preventing and promptly treating malaria, providing appropriate vaccines, and identifying ways to reach travelers whose purpose for travel is visiting friends and relatives in advance of travel can reduce the burden of travel-related illness.

Journal ArticleDOI
TL;DR: In a matched case-control study of 567 Malian children, the authors found that group O was present in only 21% of severe malaria cases compared with 44-45% of uncomplicated malaria controls and healthy controls.
Abstract: Malaria has been a major selective force on the human population, and several erythrocyte polymorphisms have evolved that confer resistance to severe malaria. Plasmodium falciparum rosetting, a parasite virulence phenotype associated with severe malaria, is reduced in blood group O erythrocytes compared with groups A, B, and AB, but the contribution of the ABO blood group system to protection against severe malaria has received little attention. We hypothesized that blood group O may confer resistance to severe falciparum malaria through the mechanism of reduced rosetting. In a matched case-control study of 567 Malian children, we found that group O was present in only 21% of severe malaria cases compared with 44–45% of uncomplicated malaria controls and healthy controls. Group O was associated with a 66% reduction in the odds of developing severe malaria compared with the non-O blood groups (odds ratio 0.34, 95% confidence interval 0.19–0.61, P < 0.0005, severe cases versus uncomplicated malaria controls). In the same sample set, P. falciparum rosetting was reduced in parasite isolates from group O children compared with isolates from the non-O blood groups (P = 0.003, Kruskal–Wallis test). Statistical analysis indicated a significant interaction between host ABO blood group and parasite rosette frequency that supports the hypothesis that the protective effect of group O operates through the mechanism of reduced P. falciparum rosetting. This work provides insights into malaria pathogenesis and suggests that the selective pressure imposed by malaria may contribute to the variable global distribution of ABO blood groups in the human population.

Journal ArticleDOI
TL;DR: Atovaquone/proguanil is an antimalarial combination with good efficacy and tolerability as prophylaxis and for treatment, and the artemisinin derivatives have remarkable efficacy and an excellent safety record.
Abstract: Antimalarial drug toxicity is viewed differently depending upon whether the clinical indication is for malaria treatment or prophylaxis. In the treatment of Plasmodium falciparum malaria, which has a high mortality if untreated, a greater risk of adverse reactions to antimalarial drugs is inevitable. As chloroquine resistance has become widespread, alternative agents may be used in treatment regimens, however, the toxicity of these antimalarial agents should be considered. Quinine is the mainstay for treating severe malaria due to its rare cardiovascular or CNS toxicity, but its hypoglycemic effect may be problematic. Mefloquine can cause dose-related serious neuropsychiatric toxicity and pyrimethamine-dapsone is associated with agranulocytosis, especially if the recommended dose is exceeded. Pyrimethamine-sulfadoxine and amodiaquine are associated with a relatively high incidence of potentially fatal reactions, and are no longer recommended for prophylaxis. Atovaquone/proguanil is an antimalarial combination with good efficacy and tolerability as prophylaxis and for treatment. The artemisinin derivatives have remarkable efficacy and an excellent safety record. Prescribing in pregnancy is a particular problem for clinicians because the risk-benefit ratio is often very unclear.

Journal ArticleDOI
TL;DR: Re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden and it is suggested that both school-age children and pregnant women would benefit from an integrated approach to malaria and helminth control.
Abstract: Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review, we adopted an empirical approach to studying the geography and epidemiology of co-infection and associations between patterns of co-infection and hemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hook- worm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women— groups which have the highest risk of anemia—would benefit from an integrated approach to malaria and helminth control.

Journal ArticleDOI
20 Jun 2007-JAMA
TL;DR: In this paper, the effect of increasing resistance to sulfadoxine-pyrimethamine on the efficacy of intermittent preventive therapy (IPT) during pregnancy in Africa was determined.
Abstract: ContextIn malaria-endemic regions, strategies to control malaria during pregnancy rely on case management of malaria illness and anemia, and preventive measures such as insecticide-treated nets and intermittent preventive therapy (IPT).ObjectiveTo determine the effect of increasing resistance to sulfadoxine-pyrimethamine on the efficacy of IPT during pregnancy in Africa.Data Sources and Study SelectionThe 6 databases of MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane CENTRAL, and the trial register and bibliographic database of the Malaria in Pregnancy Library were searched for relevant studies regardless of language, published between 1966 and December 2006. The reference lists of all trials identified were searched and researchers were contacted about relevant data. Nine trials of IPT with sulfadoxine-pyrimethamine during pregnancy in Africa were identified and matched by year and location with treatment studies of sulfadoxine-pyrimethamine among symptomatic children.Data ExtractionData on the efficacy of IPT with sulfadoxine-pyrimethamine on placental and peripheral malaria, birth weight, and hemoglobin level/anemia were independently abstracted by 2 investigators. Sulfadoxine-pyrimethamine resistance was defined as the proportion of total treatment failures in symptomatic children by day 14.Data SynthesisFour trials compared 2-dose IPT with sulfadoxine-pyrimethamine to case management or placebo in women during their first or second pregnancy. The IPT reduced placental malaria (relative risk [RR], 0.48; 95% CI, 0.35-0.68), low birth weight (RR, 0.71; 95% CI, 0.55-0.92), and anemia (RR, 0.90; 95% CI, 0.81-0.99). The effect did not vary by sulfadoxine-pyrimethamine resistance levels (range, 19%-26%). Efficacy of IPT with sulfadoxine-pyrimethamine was lower among women using insecticide-treated nets. Three trials compared 2-dose with monthly IPT with sulfadoxine-pyrimethamine during pregnancy. Among HIV-positive women in their first or second pregnancy, monthly IPT resulted in less placental malaria (RR, 0.34; 95% CI, 0.18-0.64) and higher birth weight (mean difference, 112 g; 95% CI, 19-205 g) over the range of sulfadoxine-pyrimethamine resistance tested (8%-39%). Among HIV-negative women, there was no conclusive additional effect of monthly dosing (2 trials; 24% and 39% resistance).ConclusionsIn areas in which 1 of 4 treatments with sulfadoxine-pyrimethamine fail in children by day 14, the 2-dose IPT with sulfadoxine-pyrimethamine regimen continues to provide substantial benefit to HIV-negative semi-immune pregnant women. However, more frequent dosing is required in HIV-positive women not using cotrimoxazole prophylaxis for opportunistic infections.

Journal ArticleDOI
TL;DR: Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests, and the treatment of choice for severe or complicated malaria is currently an infusion of intravenous quinine, which is more effective in treating severe malaria in selected situations.

Journal ArticleDOI
TL;DR: Low-level infection seems to be common across malaria-endemic areas, often as complex mixed infections, and understanding these interactions could have an important influence on the deployment of interventions such as malaria vaccines.

Journal ArticleDOI
TL;DR: Evidence is provided of a changing disease burden on the Kenyan coast and that the most parsimonious explanation is an expansion in the coverage of interventions such as the use of insecticide-treated nets and the availability of anti-malarial medicines.
Abstract: Background There is only limited information on the health impact of expanded coverage of malaria control and preventative strategies in Africa.

Journal Article
TL;DR: Evidence of the clinical implications and burden of malaria in pregnancy is reviewed and Meta-analyses of intervention trials suggest that successful prevention of P falciparum infections during pregnancy reduces the risk of severe maternal anaemia, low birthweight, and perinatal mortality among paucigravidae.

Journal ArticleDOI
TL;DR: Large‐scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years, suggest that targeting larvae, particularly in human‐made habitats, can significantly reduce malaria transmission in appropriate settings.
Abstract: Malaria vector control targeting the larval stages of mosquitoes was applied successfully against many species of Anopheles (Diptera: Culicidae) in malarious countries until the mid-20th Century. Since the introduction of DDT in the 1940s and the associated development of indoor residual spraying (IRS), which usually has a more powerful impact than larval control on vectorial capacity, the focus of malaria prevention programmes has shifted to the control of adult vectors. In the Afrotropical Region, where malaria is transmitted mainly by Anopheles funestus Giles and members of the Anopheles gambiae Giles complex, gaps in information on larval ecology and the ability of An. gambiae sensu lato to exploit a wide variety of larval habitats have discouraged efforts to develop and implement larval control strategies. Opportunities to complement adulticiding with other components of integrated vector management, along with concerns about insecticide resistance, environmental impacts, rising costs of IRS and logistical constraints, have stimulated renewed interest in larval control of malaria vectors. Techniques include environmental management, involving the temporary or permanent removal of anopheline larval habitats, as well as larviciding with chemical or biological agents. This present review covers large-scale trials of anopheline larval control methods, focusing on field studies in Africa conducted within the past 15 years. Although such studies are limited in number and scope, their results suggest that targeting larvae, particularly in human-made habitats, can significantly reduce malaria transmission in appropriate settings. These approaches are especially suitable for urban areas, where larval habitats are limited, particularly when applied in conjunction with IRS and other adulticidal measures, such as the use of insecticide treated bednets.

Journal ArticleDOI
TL;DR: Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria, however, diHydroart Artemisin in-pipersaquine provided greater post-treatment prophylaxis than did artem ether- lumefanrine, reducing P falciparum reinfections and P vivax recurrences.


Journal ArticleDOI
TL;DR: The Lubombo Spatial Development Initiative is a joint development program between the governments of Mozambique, Swaziland, and South Africa, which includes malaria control as a core component of the initiative and provides a strong argument for investment in regional malaria control.
Abstract: The Lubombo Spatial Development Initiative is a joint development program between the governments of Mozambique, Swaziland, and South Africa, which includes malaria control as a core component of the initiative. Vector control through indoor residual spraying (IRS) was incrementally introduced in southern Mozambique between November 2000 and February 2004. Surveillance to monitor its impact was conducted by annual cross-sectional surveys to assess the prevalence of Plasmodium falciparum infection, entomologic monitoring, and malaria case notification in neighboring South Africa and Swaziland. In southern Mozambique, there was a significant reduction in P. falciparum prevalence after the implementation of IRS, with an overall relative risk of 0.74 for each intervention year (P < 0.001), ranging from 0.66 after the first year to 0.93 after the fifth intervention year. Substantial reductions in notified malaria cases were reported in South Africa and Swaziland over the same period. The success of the program in reducing malaria transmission throughout the target area provides a strong argument for investment in regional malaria control.

Journal ArticleDOI
23 May 2007-JAMA
TL;DR: Despite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials.
Abstract: ContextImproving the accuracy of malaria diagnosis with rapid antigen-detection diagnostic tests (RDTs) has been proposed as an approach for reducing overtreatment of malaria in the current era of widespread implementation of artemisinin-based combination therapy in sub-Saharan Africa.ObjectiveTo assess the association between use of microscopy and RDT and the prescription of antimalarials.Design, Setting, and ParticipantsCross-sectional, cluster sample survey, carried out between March and May 2006, of all outpatients treated during 1 working day at government and mission health facilities in 4 sentinel districts in Zambia.Main Outcome MeasureProportions of patients undergoing malaria diagnostic procedures and receiving antimalarial treatment.ResultsSeventeen percent of the 104 health facilities surveyed had functional microscopy, 63% had RDTs available, and 73% had 1 or more diagnostics available. Of patients with fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%) treated in health facilities with malaria diagnostics were tested and 44.6% had positive test results. Of patients with negative blood smear results, 58.4% (95% CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI, 16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did not have diagnostic tests done, 65.9% were also prescribed antimalarials. In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed to a large proportion of febrile patients with a positive diagnostic test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%-100.0%]), but also to some of those with a negative diagnostic test result (blood smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]).ConclusionsDespite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials. Provision of new tools to reduce inappropriate use of new expensive antimalarial treatments must be accompanied by a major change in clinical treatment of patients presenting with fever but lacking evidence of malaria infection.

Journal ArticleDOI
TL;DR: Cerebral malaria may be a major cause of cognitive impairment in children in sub-Saharan Africa and cognitive deficits in children with cerebral malaria are more likely for those who have multiple seizures before effective treatment for cerebral malaria.
Abstract: OBJECTIVE. This study was conducted to assess prospectively the frequency of cognitive deficits in children with cerebral malaria. METHODS. Cognitive testing in the areas of working memory, attention, and learning was performed for Ugandan children 5 to 12 years of age with cerebral malaria (n = 44), children with uncomplicated malaria (n = 54), and healthy community children (n = 89) at admission and 3 and 6 months later. RESULTS. Six months after discharge, 21.4% of children with cerebral malaria had cognitive deficits, compared with 5.8% of community children. Deficits were seen in the areas of working memory (11.9% vs 2.3%) and attention (16.7% vs 2.3%). Children with cerebral malaria had a 3.7-fold increased risk of a cognitive deficit, compared with community children, after adjustment for age, gender, nutritional status, school level, and home environment. Among children with cerebral malaria, those with a cognitive deficit had more seizures before admission (mean: 4.1 vs 2.2) and a longer duration of coma (43.6 vs 30.5 hours), compared with those without a deficit. Children with uncomplicated malaria did not have an increased frequency of cognitive deficits. CONCLUSIONS. Cerebral malaria may be a major cause of cognitive impairment in children in sub-Saharan Africa. Cognitive deficits in children with cerebral malaria are more likely for those who have multiple seizures before effective treatment for cerebral malaria.

Journal ArticleDOI
TL;DR: A summary of the disease, the life cycle of the parasite, information relating to the genome and proteome of the species lethal to humans, Plasmodium falciparum, together with other recent developments in the field are included.
Abstract: Malaria is caused by protozoan parasites of the genus Plasmodium and is a major cause of mortality and morbidity worldwide. These parasites have a complex life cycle in their mosquito vector and vertebrate hosts. The primary factors contributing to the resurgence of malaria are the appearance of drug-resistant strains of the parasite, the spread of insecticide-resistant strains of the mosquito and the lack of licensed malaria vaccines of proven efficacy. This minireview includes a summary of the disease, the life cycle of the parasite, information relating to the genome and proteome of the species lethal to humans, Plasmodium falciparum, together with other recent developments in the field.

Journal ArticleDOI
TL;DR: Lack of research, evidence of failing chloroquine efficacy, and no licensed primary chemoprophylactic agent protects travelers from relapse demonstrate the lack of research on P. vivax.

Journal ArticleDOI
TL;DR: The results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children, and give fresh perspectives on malaria protection by G6 PD deficiency as an X-linked trait.
Abstract: Background Glucose-6-phosphate dehydrogenase (G6PD) is important in the control of oxidant stress in erythrocytes, the host cells for Plasmodium falciparum. Mutations in this enzyme produce X- linked deficiency states associated with protection against malaria, notably in Africa where the Aform of G6PD deficiency is widespread. Some reports have proposed that heterozygous females with mosaic populations of normal and deficient erythrocytes (due to random X chromosome inactivation) have malaria resistance similar to or greater than hemizygous males with populations of uniformly deficient erythrocytes. These proposals are paradoxical, and they are not consistent with currently hypothesized mechanisms of protection. Methods and Findings We conducted large case-control studies of the Aform of G6PD deficiency in cases of severe or uncomplicated malaria among two ethnic populations of rural Mali, West Africa, where malaria is hyperendemic. Our results indicate that the uniform state of G6PD deficiency in hemizygous male children conferred significant protection against severe, life-threatening malaria, and that it may have likewise protected homozygous female children. No such protection was evident from the mosaic state of G6PD deficiency in heterozygous females. We also found no significant differences in the parasite densities of males and females with differences in G6PD status. Pooled odds ratios from meta-analysis of our data and data from a previous study confirmed highly significant protection against severe malaria in hemizygous males but not in heterozygous females. Among the different forms of severe malaria, protection was principally evident against cerebral malaria, the most frequent form of life- threatening malaria in these studies.

Journal ArticleDOI
01 Jul 2007-Blood
TL;DR: The recent clinical and experimental studies of malaria are summarized to highlight similarities and differences in human and mouse pathology that result in anemia and so inform the use of mouse models in the study of severe malarial anemia in humans.

Journal ArticleDOI
TL;DR: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic, however, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected inChildren with severe malarial anemia.
Abstract: Background. Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. Methods. From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. Results. Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. Conclusions. Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.