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Background: Rapid declines in malaria prevalence, cases, and deaths have been achieved globally during the past 15 years because of improved access to first-line treatment and vector control. We aimed to assess the intervention coverage needed to achieve further gains over the next 15 years., Methods: We used a mathematical model of the transmission of Plasmodium falciparum malaria to explore the potential effect on case incidence and malaria mortality rates from 2015 to 2030 of five different intervention scenarios: remaining at the intervention coverage levels of 2011-13 (Sustain), for which coverage comprises vector control and access to treatment; two scenarios of increased coverage to 80% (Accelerate 1) and 90% (Accelerate 2), with a switch from quinine to injectable artesunate for management of severe disease and seasonal malaria chemoprevention where recommended for both Accelerate scenarios, and rectal artesunate for pre-referral treatment at the community level added to Accelerate 2; a near-term innovation scenario (Innovate), which included longer-lasting insecticidal nets and expansion of seasonal malaria chemoprevention; and a reduction in coverage to 2006-08 levels (Reverse). We did the model simulations at the first administrative level (ie, state or province) for the 80 countries with sustained stable malaria transmission in 2010, accounting for variations in baseline endemicity, seasonality in transmission, vector species, and existing intervention coverage. To calculate the cases and deaths averted, we compared the total number of each under the five scenarios between 2015 and 2030 with the predicted number in 2015, accounting for population growth., Findings: With an increase to 80% coverage, we predicted a reduction in case incidence of 21% (95% credible intervals [CrI] 19-29) and a reduction in mortality rates of 40% (27-61) by 2030 compared with 2015 levels. Acceleration to 90% coverage and expansion of treatment at the community level was predicted to reduce case incidence by 59% (Crl 56-64) and mortality rates by 74% (67-82); with additional near-term innovation, incidence was predicted to decline by 74% (70-77) and mortality rates by 81% (76-87). These scenarios were predicted to lead to local elimination in 13 countries under the Accelerate 1 scenario, 20 under Accelerate 2, and 22 under Innovate by 2030, reducing the proportion of the population living in at-risk areas by 36% if elimination is defined at the first administrative unit. However, failing to maintain coverage levels of 2011-13 is predicted to raise case incidence by 76% (Crl 71-80) and mortality rates by 46% (39-51) by 2020., Interpretation: Our findings show that decreases in malaria transmission and burden can be accelerated over the next 15 years if the coverage of key interventions is increased., Funding: UK Medical Research Council, UK Department for International Development, the Bill & Melinda Gates Foundation, the Swiss Development Agency, and the US Agency for International Development., Competing Interests: Declaration of interests JTG reports grants from the UK Medical Research Council (MRC) during the study. ACG reports grants from the Bill & Melinda Gates Foundation and the MRC during the study; and grants from the Malaria Vaccine Initiative, Medicines for Malaria Venture, the Integrated Vector Control Consortium, the Wellcome Trust, National Institutes of Health, and WHO, and other financial support from Oxford Policy Management, the UK Department for International Development, The Global Fund for AIDs, Tuberculosis, and Malaria, and non-financial support from GlaxoSmithKline, outside the submitted work. All other authors declare no competing interests., (Copyright © Griffin et al. Open Access article distributed under the terms of CC BY. 2015. World Health Organization; licensee Elsevier. This is an Open Access article published without any waiver of WHO's privileges and immunities under international law, convention, or agreement. This article should not be reproduced for use in association with the promotion of commercial products, services, or any legal entity. There should be no suggestion that WHO endorses any specific organisation or products. The use of the WHO logo is not permitted. This notice should be preserved along with the Article's original URL.)

Background: To control malaria, the Rwandan government and its partners distributed insecticide-treated nets (ITN) and made artemisinin-based combination therapy (ACT) widely available from 2005 onwards. The impact of these interventions on malaria cases, admissions and deaths was assessed using data from district hospitals and household surveys., Methods: District records of ITN and ACT distribution were reviewed. Malaria and non-malaria indictors in 30 district hospitals were ascertained from surveillance records. Trends in cases, admissions and deaths for 2000 to 2010 were assessed by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period, 2000-2005. Changes were estimated by comparing trends in post-intervention (2006-2010) with that of pre-intervention (2000-2005) period. All-cause deaths in children under-five in household surveys of 2005 and 2010 were also reviewed to corroborate with the trends of deaths observed in hospitals., Results: The proportion of the population potentially protected by ITN increased from nearly zero in 2005 to 38% in 2006, and 76% in 2010; no major health facility stock-outs of ACT were recorded following their introduction in 2006. In district hospitals, after falling during 2006-2008, confirmed malaria cases increased in 2009 coinciding with decreased potential ITN coverage and declined again in 2010 following an ITN distribution campaign. For all age groups, from the pre-intervention period, microscopically confirmed cases declined by 72%, (95% Confidence Interval [CI], 12-91%) in 2010, slide positivity rate declined 58%, (CI, 47%-68%), malaria inpatient cases declined 76% (CI, 49%-88%); and malaria deaths declined 47% (CI, 47%-81%). In children below five years of age, malaria inpatients decreased 82% (CI, 61%-92%) and malaria hospital deaths decreased 77% (CI, 40%-91%). Concurrently, outpatient cases, admissions and deaths due to non-malaria diseases in all age groups either increased or remained unchanged. Rainfall and temperature remained favourable for malaria transmission. The annual all-cause mortality in children under-five in household surveys declined from 152 per 1,000 live births during 2001-2005, to 76 per 1,000 live births in 2006-2010 (55% decline). The five-year cumulative number of all-cause deaths in hospital declined 28% (8,051 to 5,801) during the same period., Conclusions: A greater than 50% decline in confirmed malaria cases, admissions and deaths at district hospitals in Rwanda since 2005 followed a marked increase in ITN coverage and use of ACT. The decline occurred among both children under-five and in those five years and above, while hospital utilization increased and suitable conditions for malaria transmission persisted. Declines in malaria indicators in children under 5 years were more striking than in the older age groups. The resurgence in cases associated with decreased ITN coverage in 2009 highlights the need for sustained high levels of anti-malarial interventions in Rwanda and other malaria endemic countries.

Background: Intermittent Preventive Treatment of malaria in infants using sulfadoxine-pyrimethamine (SP-IPTi) is recommended by WHO for implementation in settings where resistance to SP is not high. Here we examine the relationship between the protective efficacy of SP-IPTi and measures of SP resistance., Methods and Results: We analysed the relationship between protective efficacy reported in the 7 SP-IPTi trials and contemporaneous data from 6 in vivo efficacy studies using SP and 7 molecular studies reporting frequency of dhfr triple and dhps double mutations within 50 km of the trial sites. We found a borderline significant association between frequency of the dhfr triple mutation and protective efficacy to 12 months of age of SP-IPTi. This association is significantly biased due to differences between studies, namely number of doses of SP given and follow up times. However, fitting a simple probabilistic model to determine the relationship between the frequency of the dhfr triple, dhps double and dhfr/dhps quintuple mutations associated with resistance to SP and protective efficacy, we found a significant inverse relationship between the dhfr triple mutation frequency alone and the dhfr/dhps quintuple mutations and efficacy at 35 days post the 9 month dose and up to 12 months of age respectively., Conclusions: A significant relationship was found between the frequency of the dhfr triple mutation and SP-IPTi protective efficacy at 35 days post the 9 month dose. An association between the protective efficacy to 12 months of age and dhfr triple and dhfr/dhps quintuple mutations was found but should be viewed with caution due to bias. It was not possible to define a more definite relationship based on the data available from these trials.

Background: Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials., Methods: We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs., Findings: In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36-4.03 based on trial specific data and USD 0.68-2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still remain highly cost effective in all sites where IPTi had a statistically significant effect on clinical malaria., Conclusions: IPTi delivered alongside the EPI is a highly cost effective intervention against clinical malaria with a range of drugs in a range of malaria transmission settings. Where IPTi did not have a statistically significant impact on malaria, generally in low transmission sites, it was not cost effective.

Background: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects., Methods: Between March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months)., Principal Findings: 1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (-5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (-6.9, 50.8); 23.1% (-11.9, 47.2); and 11.4% (-28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated., Conclusions: These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy.

Background: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa., Methods: We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo., Findings: The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30.3% (95% CI 19.8-39.4, p<0.0001) against clinical malaria, 21.3% (8.2-32.5, p=0.002) against the risk of anaemia, 38.1% (12.5-56.2, p=0.007) against hospital admissions associated with malaria parasitaemia, and 22.9% (10.0-34.0, p=0.001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1.05, 95% CI 0.72-1.54, p=0.79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group., Interpretation: IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control., Funding: Bill & Melinda Gates Foundation.

Background: IPTi delivered through EPI has been shown to reduce the incidence of clinical malaria by 20-59%. However, new health interventions can only be effective if they are also socially and culturally acceptable. It is also crucial to ensure that attitudes to IPTi do not negatively influence attitudes to and uptake of immunization, or that people do not misunderstand IPTi as immunization against malaria and neglect other preventive measures or delay treatment seeking., Methods: These issues were studied in five African countries in the context of clinical trials and implementation studies of IPTi. Mixed methods were used, including structured questionnaires (1,296), semi-structured interviews (168), in-depth interviews (748) and focus group discussions (95) with mothers, fathers, health workers, community members, opinion leaders, and traditional healers. Participant observation was also carried out in the clinics., Results: IPTi was widely acceptable because it resonated with existing traditional preventive practices and a general concern about infant health and good motherhood. It also fit neatly within already widely accepted routine vaccination. Acceptance and adherence were further facilitated by the hierarchical relationship between health staff and mothers and by the fact that clinic attendance had a social function for women beyond acquiring health care. Type of drug and regimen were important, with newer drugs being seen as more effective, but potentially also more dangerous. Single dose infant formulations delivered in the clinic seem to be the most likely to be both acceptable and adhered to. There was little evidence that IPTi per se had a negative impact on attitudes to EPI or that it had any affect on EPI adherence. There was also little evidence of IPTi having a negative impact on health seeking for infants with febrile illness or existing preventive practices., Conclusion: IPTi is generally acceptable across a wide range of settings in Africa and involving different drugs and regimens, though there is a strong preference for a single dose infant formulation. IPTi does not appear to have any negative effect on attitudes to EPI, and it is not interpreted as immunization against malaria.

Background: Because of the emergence of chloroquine resistance in Mali, artemether-lumefantrine (AL) or artesunate-amodiaquine (AS+AQ) are recommended as first-line therapy for uncomplicated malaria, but have not been available in Mali until recently because of high costs., Methods: From July 2005 to January 2006, a randomized open-label trial of three oral antimalarial combinations, namely AS+AQ, artesunate plus sulphadoxine-pyrimethamine (AS+SP), and amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP), was conducted in Faladje, Mali. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish new from recrudescent Plasmodium falciparum infections., Results: 397 children 6 to 59 months of age with uncomplicated Plasmodium falciparum malaria were enrolled, and followed for 28 days to assess treatment efficacy. Baseline characteristics were similar in all three treatment groups. The uncorrected rates of adequate clinical and parasitologic response (ACPR) were 55.7%, 90.8%, and 97.7% in AS+AQ, AS+SP, and AQ+SP respectively (p < 0.001); after PCR correction ACPR rates were similar among treatment groups: 95.4%, 96.9%, and 99.2% respectively (p = 0.17). Mean haemoglobin concentration increased across all treatment groups from Day 0 (9.82 +/- 1.68 g/dL) to Day 28 (10.78 +/- 1.49 g/dL) (p < 0.001), with the greatest improvement occurring in children treated with AQ+SP. On Day 2, the prevalence of parasitaemia was significantly greater among children treated with AQ+SP (50.8%) than in children treated with AS+AQ (10.5%) or AS+SP (10.8%) (p < 0.001). No significant difference in gametocyte carriage was found between groups during the follow-up period., Conclusion: The combination of AQ+SP provides a potentially low cost alternative for treatment of uncomplicated P. falciparum infection in Mali and appears to have the added value of longer protective effect against new infection.

Plasmodium infection, often sub-clinical, is common in migrating sub-Saharan refugee populations. Refugees who subsequently develop clinical malaria suffer illness and exact a cost on state and local health care facilities. Untreated infection is also of public health concern because of the potential for local transmission. In response to increasing numbers of refugees originating in sub-Saharan Africa guidelines for the management of malaria in refugees migrating to the United States have been broadened and updated. The guidelines are based on available evidence-based literature and recent public health experience. These guidelines were critically reviewed, assessed, and approved by multiple National and State entities as well as outside experts. These consensus guidelines recommend that sub-Saharan African refugees relocating to the United States receive presumptive treatment of P. falciparum malaria before departure or during the domestic refugee medical screening after arrival. Presumptive therapy is not currently recommended for either non-falciparum malaria or for refugees relocating from areas outside sub-Saharan Africa.

Purpose of Review: This review summarizes recent evidence regarding the efficacy of intermittent preventive treatment with focus on infancy (IPTi) and the rationale behind such a control strategy., Recent Findings: Pooled safety and efficacy analyses of all six trials of IPTi with sulfadoxine-pyrimethamine conducted between 1999 and 2007 have demonstrated a 30% protective efficacy against clinical malaria, a 24% protective efficacy against all-cause hospital admissions, a 37% protective efficacy against malaria-related hospital admissions, and a 15% protective efficacy against anemia, all in the first year of life. Rebound in malaria following discontinuation of the intervention has not been noted in pooled analyses of the IPTi trials., Summary: Given the efficacy, excellent safety and tolerability of the intervention and the fact that it is inexpensive and easily deliverable if linked to the Expanded Programme on Immunization, IPTi-sulfadoxine-pyrimethamine appears to add a valuable tool to the malaria-control armamentarium in endemic areas of Africa. Routine monitoring of sulfadoxine-pyrimethamine efficacy will be required to guide future IPTi programme implementation. Variations of IPTi that target older children may be required for areas of Africa with highly seasonal malaria transmission.

Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering >or=2 treatment doses of sulfadoxine/pyrimethamine to pregnant women at predefined intervals after quickening (around 18-20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine use in IPTp programmes in Africa, with 2-4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/pyrimethamine - when delivered as IPTp - has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.

The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.

Background: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear., Methods: In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women., Results: Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP., Conclusions: In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted.

We estimated the frequency of clinically diagnosed Stevens-Johnson syndrome and toxic epidermal necrolysis associated with sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (CTX) in Blantyre District, Malawi. Cases were detected by passive surveillance at 22 health centers from March 2001 through September 2002. Denominators were estimated from the Malawi national census for Blantyre District and the frequency of SP and CTX use reported in five household surveys. Crude rates of adverse reactions were estimated to be 1.2 per 100,000 exposures for SP and 1.5 per 100,000 exposures for CTX. Rates were higher in adults (1.7 cases per 100,000 SP exposures and 2.6 cases per 100,000 CTX exposures) and in persons positive for human immunodeficiency virus (4.9 cases per 100,000 SP exposures and 8.4 cases per 100,000 CTX exposures). Infrequent treatment doses with SP are associated with a low risk of an adverse cutaneous reaction, and SP can be recommended for treatment of malaria in areas where P. falciparum is susceptible.

Background: Despite a broadening consensus about the effectiveness of intermittent preventive treatment (IPTp) in preventing the adverse outcomes of malaria during pregnancy, policy change to IPTp was initially limited to East Africa. In West Africa, where the policy change process for the prevention of malaria during pregnancy started much later, IPTp has been taken up swiftly., Objective: To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa., Results and Conclusion: Several factors appear to have accelerated the process: (1) recognition of the extent of the problem of malaria during pregnancy and its adverse consequences; (2) a clear, evidence-based program strategy strongly articulated by an important multilateral organization (World Health Organization); (3) subregionally generated evidence to support the proposed strategy; (4) a subregional forum for dissemination of data and discussion regarding the proposed policy changes; (5) widespread availability of the proposed intervention drug (sulfadoxine-pyrimethamine); (6) technical support from reputable and respected institutions in drafting new policies and planning for implementation; (7) donor support for pilot experiences in integrating proposed policy change into a package of preventive services; and (8) financial support for scaling up the proposed interventions.

Background: Travelers to malarious areas are at risk of acquiring malaria; however, with chemoprophylaxis and prompt, effective therapy, serious complications of infection are generally preventable. In June 2002, we investigated a report of a cluster of malaria cases among US university staff and students who visited Ghana and were reportedly adherent to appropriate malaria chemoprophylaxis., Methods: We administered a questionnaire to all participants and collected blood specimens for malaria serological examinations from those reporting malaria infection diagnosed by blood smear in Ghana., Results: Of the 33 participants, 25 completed the questionnaire. Twenty-four took a Centers for Disease Control and Prevention-recommended chemoprophylactic drug; 14 (56%) of 25 reported complete adherence to therapy. Twenty (80%) of 25 subjects reported symptoms consistent with possible malaria. Six of these persons reported a microscopic diagnosis of malaria and were treated in Ghana. Serological examination for malaria was performed using blood samples obtained from 5 of these participants; the results for all were negative, suggesting that incorrect diagnoses of malaria were made., Conclusions: Misdiagnosis of malaria made while a person is abroad may not only lead to erroneous reports of drug resistance, but it could also result in unnecessary administration of antimalarial treatment. Health care providers and public health authorities must critically evaluate reports of chemoprophylactic failures and disseminate accurate information to travelers.

Plasmodium falciparum malaria in pregnancy poses substantial risk to a pregnant woman and her neonate through anaemia and low birth weight (LBW), respectively, and is responsible for up to 35% of preventable LBW in malaria-endemic areas. Chemoprophylaxis or intermittent preventive treatment (IPT) with an effective antimalarial can ameliorate the adverse effects of malaria during pregnancy. Current guidelines from the WHO recommend that women in highly malarious areas receive IPT with an effective antimalarial. Two central considerations in evaluating drugs for use during pregnancy are safety for the mother and her foetus and effectiveness, which is determined by efficacy, cost, availability, deliverability and acceptability of the drug. These factors may be scored and potential drugs or drug combinations ranked in order of potential effectiveness for use in prevention programmes. The seven most promising regimens are all IPT, primarily because they are more easily delivered and less expensive than chemoprophylaxis. Currently, IPT with sulphadoxine-pyrimethamine (SP) is more likely to have the best overall effectiveness in preventing adverse outcomes associated with malaria in pregnancy. Its low cost, wide availability, easy deliverability and acceptability make it the clear choice in countries where efficacy of the drug remains good. For countries where resistance to SP is rising or already high, amodiaquine (alone or in combination with SP or artesunate) artesunate + SP, chlorproguanil-dapsone (with and without artesunate) and artemether-lumefantrine require urgent evaluation for use in pregnancy.

In West Africa, administration of chloroquine chemoprophylaxis during pregnancy is common, but little is known about its impact on Plasmodium falciparum infection during pregnancy. Therefore, cross-sectional studies in antenatal care clinics (ANCs) and delivery units (DUs) were conducted in Koupéla District, Burkina Faso. Chloroquine chemoprophylaxis was reported by 69% of 597 pregnant women at ANCs and by 93% of 853 women in DUs. P. falciparum peripheral parasitemia was identified in 29% of women at both ANCs and DUs. Placental parasitemia was identified in 22% of delivering women and was strongly associated with low birth weight (LBW) (risk ratio [RR], 1.7; 95% confidence interval [CI], 1.2-2.4) and prematurity (RR, 2.9; 95% CI, 1.6-5.4). In multivariate analysis, use of chemoprophylaxis was not associated with a reduction in the prevalence of placental parasitemia, LBW, or prematurity. Despite the high reported chloroquine chemoprophylaxis coverage, peripheral and placental malaria rates remain high and are associated with known adverse outcomes during pregnancy, including maternal anemia, prematurity, and LBW. Alternative prevention strategies, such as use of insecticide-treated mosquito nets and intermittent preventive treatment with more-effective antimalarials, are needed.

An abstract of the article "The global challenge of antimalarial drug resistance," by Pascal Ringwald, Amy Barrette, Charlotte Rasmussen, Robert D. Newman is presented.