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Gavi, the Vaccine Alliance, was created in 2000 to accelerate the introduction of new and underused vaccines in lower-income countries. The period 2000-15 was marked by the rapid uptake of new vaccines in more than seventy countries eligible for Gavi support. To stay focused on the poorest countries, Gavi's support phases out after countries' gross national income per capita surpasses a set threshold, which requires governments to assume responsibility for the continued financing of vaccines introduced with Gavi support. Gavi's funding will end in the period 2016-20 for nineteen countries that have exceeded the eligibility threshold. To avoid disrupting lifesaving immunization programs and to ensure the long-term sustainable impact of Gavi's investments, it is vital that governments succeed in transitioning from development assistance to domestic financing of immunization programs. This article discusses some of the challenges facing countries currently transitioning out of Gavi support, how Gavi's policies have evolved to help manage the risks involved in this process, and the lessons learned from this experience.

The Malaria Eradication Research Agenda (malERA) Consultative Group on Drugs present a research and development agenda to ensure that appropriate drugs are available for use in malaria eradication., Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.

Approximately 2 billion persons worldwide are infected with schistosomiasis and soil-transmitted helminthes (STH), many in areas where endemic malaria transmission coexists. Few data exist on associations between these infec- tions. Nested within a larger clinical trial, primigravid and secundigravid women provided blood samples for human immu- nodeficiency virus (HIV) testing and peripheral malaria films and stool and urine for evaluation of STH and Schistosoma spp. during their initial antenatal clinic visit. The most common parasitic infections were malaria (37.6%), S. haematobium (32.3%), and hookworm (14.4%); 14.2% of women were HIV-infected. S. haematobium infection was associated with lower malarial parasite densities (344 versus 557 parasites/μL blood; P < 0.05). In multivariate analysis, HIV and hook- worm infection were independently associated with malaria infection (adjusted odds ratio = 1.9 and 95% confidence interval = 1.2-3.0 for HIV; adjusted odds ratio = 1.9 and 95% confidence interval = 1.03-3.5 for hookworm). Concurrent helminthic infection had both positive and negative effects on malaria parasitemia among pregnant women in Malawi.

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 administeringor=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.

Summary 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.

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.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.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.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.

Background. Malaria during pregnancy contributes to maternal anemia and low birth weight. In East Africa, several studies have demonstrated that intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) is more efficacious than weekly chloroquine (CQ) chemoprophylaxis in preventing these adverse consequences. To our knowledge, there are no published trials evaluating IPT in West Africa. Methods. We undertook a randomized controlled trial of weekly CQ chemoprophylaxis, 2-dose IPT with CQ, and 2-dose IPT with SP; 1163 women were enrolled. Results. In multivariate analyses, when compared with weekly CQ, IPT/SP was associated with a reduction in third-trimester anemia (adjusted odds ratio [AOR], 0.49; ), placental parasitemia (AOR, 0.69; P ! .001 P p ), and low birth weight (!2500 g) (AOR, 0.69; ). The prevalence of placental infection remained .04 P p .04 unexpectedly high, even in the IPT/SP group (24.5%), possibly because of the intensity of seasonal transmission. There were no significant differences in stillbirths, spontaneous abortions, or neonatal deaths among the 3 groups. Conclusions. In Mali, IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy. These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy. In intensely seasonal transmission settings in Mali, 12 doses may be required to prevent placental reinfection prior to delivery.

Summary Background The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. Methods We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2–10 years (PrP2–10), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. Findings Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP2–10 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP2–10 20%) it was 41% (21 to 57), and at high transmission (PrP2–10 70%) the efficacy was 4% (−10 to 22). Vaccine efficacy also varied by adjuvant choice (p

To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had placental malaria, and 102 (19.9%) infants acquired HIV perinatally. Log10 HIV viral load and episiotomy or perineal tear were associated with increased perinatal HIV transmission, whereas low-density placental malaria (10,000 parasites/mL) was associated with reduced risk (adjusted relative risk [ARR] 0.4). Among women dually infected with malaria and HIV, high-density placental malaria (10,000 parasites/mL) was associated with increased risk for perinatal MTCT (ARR 2.0), compared to low-density malaria. The interaction between placental malaria and MTCT appears to be variable and complex: placental malaria that is controlled at low density may cause an increase in broad-based immune responses that protect against MTCT; uncontrolled, high-density malaria may simultaneously disrupt placental architecture and generate substantial antigen stimulus to HIV replication and increase risk for MTCT.

OBJECTIVE To evaluate the epidemiology of Giardia lamblia infection, investigate factors which might be associated with clinical manifestations and recurrence, and examine the role of copathogens in disease course. METHODS Prospective 4-year cohort study of children born in an urban slum in north-eastern Brazil. RESULTS Of 157 children followed for ≥ 3 months, 43 (27.4%) were infected with Giardia. The organism was identified in 8.8% of all stool specimens, and although found with similar frequency in non-diarrhoeal (7.4%) and diarrhoeal stools (9.7%), was more common in children with persistent (20.6%) than acute diarrhoea (7.6%, P=0.002). Recurrent or relapsing infections were common (46%). Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children. Copathogens were not associated with disease course. CONCLUSION With its protean clinical manifestations, Giardia may be associated with substantial morbidity amongst children in Brazil.

PURPOSE: To investigate the use of activated charcoal to mark the biopsy site and needle track after large-core-needle breast biopsy. MATERIALS AND METHODS: Three hundred seventy-six consecutive patients (with 383 lesions) were referred for stereotactic breast biopsy. Two hundred forty-seven lesions were carbon marked when the need for surgery was likely. Patients who underwent marking were followed up for the results of surgery or mammography performed at our institution. Specimen sizes obtained by using the carbon mark were compared with sizes of consecutive biopsy specimens obtained after hook-wire localization. RESULTS: Carbon marking was well tolerated in all cases. All 132 surgeries performed at the authors' institution were successful in removing the marked target. Specimen sizes compared favorably with sizes of comparison hook-wire localization specimens. All 68 lesions followed mammographically revealed no changes that were attributable to the use of carbon. Two minor complications were observed. Two small cancers were completely removed at needle biopsy. CONCLUSION: Carbon marking is safe and effective for marking the biopsy site and needle track created by stereotactic large-core-needle biopsy of the breast. Marking eliminates the need for postprocedural needle localization. It remains effective when small lesions have been completely removed. This technique should be considered in properly selected cases by those performing large-core-needle biopsy of the breast.

Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.

The objective of the study was to describe ambulatory health care services, determine the level of client satisfaction, and identify obstacles to care in a rural area of Mozambique. Exit surveys at 34 health clinics in Manica Province were completed on a sample of 879 adults representing between 1% and 2% of the average monthly visit totals at each clinic. Eighty-three per cent of interviewees were women. Just over half of the visits were for paediatric patients. Men were more likely to be at the clinic for their own health care needs than women (81% vs. 40%, p < 0.001). Of patients seen for acute illness, 45% were examined, 22% received preventive education, and 23% received prognostic information. Overall, 55% of interviewees believed that the service they received was good or very good, 32% rated it as fair, and 13% as poor. Satisfaction was positively associated with increased training level of the provider (p < 0.005), and shorter waiting times (p < 0.001). The most common complaints about the clinic visits were lack of adequate transportation, long waiting times, lack of physical examinations, and failure to receive prescribed medications. These findings suggest that the majority of Mozambicans interviewed are moderately satisfied with the available outpatient services in Manica. Provider training, provider availability and distribution of medicines were areas identified by respondents as needing improvement.

Summary Huge increases in funding for international health over the past two decades have led to a proliferation of donors, partnerships, and health organisations. Over the same period, the global burden of non-communicable diseases has increased absolutely and relative to communicable diseases. In this changing landscape, national programmes for the control of HIV/AIDS, tuberculosis, malaria, and neglected tropical diseases must be reinforced and adapted for three reasons: the global burden of these communicable diseases remains enormous, disease control programmes have an integral and supporting role in developing health systems, and the health benefits of these control programmes go beyond the containment of specific infections. WHO's traditional role in promoting communicable disease control programmes must also adapt to new circumstances. Among a multiplicity of actors, WHO's task is to enhance its normative role as convenor, coordinator, monitor, and standard-setter, fostering greater coherence in global health.

Background Malaria control has been dramatically scaled up the past decade, mainly thanks to increasing international donor financing since 2003. This study assessed progress up to 2010 towards global malaria impact targets, in relation to Global Fund, other donor and domestic malaria programme financing over 2003 to 2009. Methods Assessments used domestic malaria financing reported by national programmes, and Global Fund/OECD data on donor financing for 90 endemic low- and middle-income countries, WHO estimates of households owning one or more insecticide-treated mosquito net (ITN) for countries in sub-Saharan Africa, and WHO-estimated malaria case incidence and deaths in countries outside sub-Saharan Africa. Results Global Fund and other donor funding is concentrated in a subset of the highest endemic African countries. Outside Africa, donor funding is concentrated in those countries with highest malaria mortality and case incidence rates over the years 2000 to 2003. ITN coverage in 2010 in Africa, and declines in case and death rates per person at risk over 2004 to 2010 outside Africa, were greatest in countries with highest donor funding per person at risk, and smallest in countries with lowest donor malaria funding per person at risk. Outside Africa, all-source malaria programme funding over 2003 to 2009 per case averted ($56-5,749) or per death averted ($58,000-3,900,000) over 2004 to 2010 tended to be lower (more favourable) in countries with higher donor malaria funding per person at risk. Conclusions Increases in malaria programme funding are associated with accelerated progress towards malaria control targets. Associations between programme funding per person at risk and ITN coverage increases and declines in case and death rates suggest opportunities to maximize the impact of donor funding, by strategic re-allocation to countries with highest continued need.

As highlighted earlier, cost–effectiveness is only one criterion among many that influence decision-making in public health. When deciding to implement an intervention, efficiency must always be balanced with other criteria, including implementation capacity, feasibility and impact on poverty and equity.14 In the case of RTS,S/AS01, WHO will provide an updated cost–effectiveness assessment in 2015, at the time when decision-making by countries will be necessary. The status of the field of malaria vaccine cost–effectiveness does not yet support the use of simple, national-level vaccine impact or cost–effectiveness tools by country programmes.

www.thelancet.com Vol 380 August 11, 2012 559 Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ 4 Kahama-Maro J, D’Acremont V, Mtasiwa D, Genton B, Lengeler C. Low quality of routine microscopy for malaria at diff erent levels of the health system in Dar es Salaam. Malaria J 2011; 10: 332. 5 Makani J, Matuja W, Liyombo E, Snow RW, Marsh K, Warrell DA. Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description. QJM 2003; 96: 355–62. New global estimates of malaria deaths

Progress in malaria control over the past decade has been striking, with malaria mortality rates falling by approximately one quarter globally and more than a third in the World Health Organization African Region. In the accompanying paper, Cohen et al. demonstrate the potential fragility of these gains, comprehensively describing malaria resurgences that have occurred over the past 80 or so years. They found that the vast majority of resurgences were due, at least in part, to the weakening of malaria control programmes; resource constraints were the most commonly identified factor. Their findings are timely and compelling, demonstrating that global efforts will be wasted if the required resources are not secured to achieve and maintain universal access to life-saving malaria prevention and control tools. The greatest threats to current malaria control efforts are not biological, but financial. The increases in funding for malaria over the past decade, while impressive, still fall far short of the nearly $6 billion dollars required annually. Domestic spending by endemic country governments on malaria specifically, and health more generally, could go a long way towards filling the projected funding gap. However, external funding is also essential, and the global community needs to work together to ensure full funding of the Global Fund to Fight AIDS, Tuberculosis, and Malaria, which has been the single largest source of malaria funding over the past decade. This year, on April 25th, World Malaria Day will be celebrated with the theme Sustain Gains, Save Lives: Invest in Malaria. The review by Cohen et al. suggests one possible future if such investment is not made. However, with sufficient support, malaria resurgences can be relegated to history.

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.

To determine the frequency of the parasitic pathogens in human immunodeficiency virus (HIV)-infected patients in a developing world setting 295 stool specimens were examined from 166 HIV-positive patients (49% with AIDS) at Sao Jose Hospital Fortaleza Brazil from September 1990 to March 1992. Significantly more patients with diarrhea (85%) than without (66%) had AIDS or AIDS-related complex (ARC) (p < 0.005). Of the potential parasitic causes of diarrhea only Cryptosporidium parvum and microsporidia were significantly associated with diarrheal disease. Infections with C. parvum but not microsporidia were associated with the rainy season (p < 0.005). Thus C. parvum and microsporidia are the most common intestinal parasites associated with diarrhea in an HIV-infected population in Brazil and are associated with advanced HIV disease. The association of C. parvum infections with the rainy season suggests that contaminated water may be important in its transmission; however the source of human microsporidia requires further investigation. (authors)

Since the 1970s, when Chinese researchers demonstrated the artemisinins' antimalarial potency, artemisinin-based combination therapy has become key to malaria control. But reduced susceptibility of Plasmodium falciparum to artemisinin is now being seen in some places.

Pedro Alonso and colleagues introduce the Malaria Eradication Research Agenda (malERA) initiative and the set of articles published in this PLoS Medicine Supplement that distill the research questions key to malaria eradication., The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda—primarily directed towards reducing morbidity and mortality—with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.

Cryptosporidium is an important cause of diarrheal disease in children worldwide. To elucidate the environmental sources of this parasite, we selected an urban slum in Fortaleza, Brazil, a community with a known high incidence of cryptosporidiosis, and examined both stool smears from household animals (n = 127) and filtrates from local water sources (n = 18) for Cryptosporidium oocysts. Because previous work in this community has demonstrated the seasonal nature of human infection with Cryptosporidium, collections were made separately for the dry and rainy seasons. Of the 64 stools collected during the dry season (September-December 1990), four (6.3%) were positive by acid-fast staining for Cryptosporidium. Of the 63 rainy season samples (March-May 1991), nine (14.3%) were positive. Overall, oocysts were detected in 13 (10.2%) of 127 animal stool samples. Freshwater samples were obtained from a variety of sources including open and closed wells, and running city water and then processed. Four of 18 samples (22.2%), including a sample from city water were positive by at least one of two staining techniques (acid-fast and immunofluorescence). In summary, animals may serve as a reservoir of Cryptosporidium, with potential for the contamination of immediate household water sources. These findings may help to explain the high incidence of cryptosporidiosis among infants in this impoverished community.

Although substantial progress has been made in controlling malaria, Robert Newman says wider investment will be essential for success

BackgroundIntermittent 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.MethodsWe 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.FindingsIn 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.ConclusionsIPTi 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 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.

We conducted a health facility-based survey of patients with fever during malaria transmission season to determine the proportion with laboratory-confirmed malaria in Luanda, Angola. We enrolled 864 patients at 30 facilities; each underwent a blood film for malaria and a questionnaire. Only 3.6% had a positive blood film. When stratified by distance of the facility to city center (< 15 km and ³ 15 km), the proportions were 1.5% (9/615) and 8.8% (22/249), respec- tively ( P < 0.0001). Of patients traveling outside Luanda in the preceding 3 months, 6.8% (6/88) had malaria, compared with 3.2% (26/776) not traveling ( P = 0.13). Children < 5 years of age were less likely to have malaria (2.4%; 12/510) than children ages 5-14 (8.7%; 9/104) and adults (4.0%; 10/250) ( P = 0.03). The prevalence of laboratory-confirmed malaria in febrile patients in Luanda is very low, but increases with distance from the urban center. Prevention and treatment should be focused in surrounding rural areas.

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.

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.

In December 2005 and March 2006, Niger conducted nationwide integrated campaigns to distribute polio vaccine and long lasting insecticide-treated nets (LLINs) to children5 years of age. We evaluated the campaign effectiveness, net retention, insecticide-treated net (ITN) ownership, and usage.Two nationwide cross-sectional surveys in January 2006 (dry season) and September 2006 (rainy season), using a stratified two-stage cluster sampling design. We mapped selected communities, selected households by simple random sampling, and administered questionnaires by interviewers using personal digital assistants.The first survey showed that ITN ownership in all households was 6.3% prior to the campaign, increasing to 65.1% after the campaign in the second survey. The second survey also showed that 73.4% of households with children5 received an LLIN and that 97.7% of households that receivedor = one LLIN retained it. The wealth equity ratio for ITN ownership in households with children5 increased from 0.17 prior to the campaign to 0.79 afterward. During the dry season, 15.4% of all children5 and 11.3% of pregnant women slept under an ITN, while during rainy season, 55.5% of children5 and 48.2% of pregnant women slept under an ITN.Free distribution during the integrated campaign rapidly increased ITN ownership and decreased inequities between those in the highest and lowest wealth quintiles. Retention of ITNs was very high, and usage was high during malaria transmission season. However, ITN ownership and usage by vulnerable groups continues to fall short of RBM targets, and additional strategies are needed to increase ownership and usage.

Data on the relationship between the two genotypes of Giardia duodenalis that infect humans, assemblages A and B, their clinical presentation and intestinal inflammation are limited. We analyzed 108 stool samples previously collected for a diarrhoeal study among Brazilian children, representing 71 infections in 47 children. Assemblage B was most prevalent, accounting for 43/58 (74.1%) infections, while assemblage A accounted for 9/58 (15.5%) infections and 6/58 (10.3%) infections were mixed (contained both assemblage A and B). There was no significant difference in diarrhoeal symptoms experienced during assemblage A, B or mixed infections. Children with assemblage B demonstrated greater variability in G. duodenalis cyst shedding but at an overall greater level (n=43, mean 3.6 x 10(5), range 5.3 x 10(2)-2.5 x 10(6)cysts/ml) than children infected with assemblage A (n=9, mean 1.4 x 10(5), range 1.5 x 10(4)-4.6 x 10(5)cysts/ml; P=0.009). Children with mixed infections shed more cysts (mean 8.3 x 10(5), range 3.1 x 10(4)-2.8 x 10(6)cysts/ml) than children with assemblage A or B alone (P=0.069 and P=0.046 respectively). This higher rate of cyst shedding in children with assemblage B may promote its spread, accounting for its increased incidence. Additionally, second and third infections had decreasing faecal lactoferrin, suggesting some protection against severity, albeit not against infection, by prior infection.

Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to or from areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.This report summarizes cases in persons with onset of illness in 2005 and summarizes trends during previous years.Malaria cases confirmed by blood film or polymerase chain reaction (PCR) are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report.CDC received reports of 1,528 cases of malaria, including seven fatal cases, with an onset of symptoms in 2005 among persons in the United States or one of its territories. This number represents an increase of 15.4% from the 1,324 cases reported for 2004. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 48.6%, 22.1%, 3.5%, and 2.5% of cases, respectively. Twelve patients (0.8% of total) were infected by two or more species. The infecting species was unreported or undetermined in 22.6% of cases. Compared with 2004, the largest increases in cases came from the Americas (23.1%; n = 213) and Asia and the Middle East (18.6%; n = 204). On the basis of estimated volume of travel, the highest estimated case rates of malaria among travelers occurred among those returning from West Africa. Of 870 U.S. civilians who acquired malaria abroad, only 160 (18.4%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Two patients became infected in the United States, both attributed to congenital transmission; both were infected with P. vivax. Seven deaths were attributed to malaria, all caused by infection with P. falciparum.The 15.4% increase in malaria cases in 2005, compared with 2004, resulted primarily from increases in the number of cases reported from Asia and the Middle East and from the Americas. This increase might in part reflect more complete reporting and in part increased travel to malarious areas. No change was noted in proportions of cases from other areas of the world, or in species responsible for the infection. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. U.S. civilians who traveled to West Africa had the highest estimated relative case rate.Additional investigations were conducted for the seven fatal cases and two infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include at least one blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline (telephone 770-488-7788). Recommendations for malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

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.

The World Health Organization recommends that pregnant women in malaria-endemic areas receiveor= 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 withor= 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, P0.0001 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.

Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.This report summarizes cases in persons with onset of illness in 2004 and summarizes trends during previous years.Malaria cases confirmed by blood film are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report.CDC received reports of 1,324 cases of malaria, including four fatal cases, with an onset of symptoms in 2004 among persons in the United States or one of its territories. This number represents an increase of 3.6% from the 1,278 cases reported for 2003. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 49.6%, 23.8%, 3.6%, and 2.0% of cases, respectively. Seventeen patients (1.3% of total) were infected by two or more species. The infecting species was unreported or undetermined in 262 (19.8%) cases. Compared with 2003, the number of reported malaria cases acquired in the Americas (n = 173) increased 17.7%, whereas the number of cases acquired in Asia (n = 172) and Africa (n = 809) decreased 2.8% and 3.7%, respectively. Of 775 U.S. civilians who acquired malaria abroad, only 160 (20.6%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Four patients became infected in the United States; three cases were attributed to congenital transmission and one to laboratory-related mosquitoborne transmission. Four deaths were attributed to malaria, including two caused by P. falciparum, one by P. vivax, and one by a mixed infection with P. falciparum and P. malariae.The 3.6% increase in malaria cases in 2004, compared with 2003, resulted primarily from an increase in the number of cases acquired in the Americas but was offset by a decrease in the number of cases acquired in Africa and Asia. This limited increase might reflect local changes in disease transmission, increased travel to regions in which malaria is endemic, or fluctuations in reporting to state and local health departments. These changes likely reflect expected variation in annual reporting and should not be interpreted as indicating a longer-term trend. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria.Additional investigations were conducted for the four fatal cases and four infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline at telephone 770-488-7788. Recommendations concerning malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

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.

Cryptosporidium is an important cause of infectious diarrhoea worldwide, but little is known about the course of illness when infected with different species. Over a period of 5 years, Cryptosporidium was identified in the stools of 58 of 157 children prospectively followed from birth in an urban slum (favela) in northeast Brazil. Forty isolates were available for quantification and 42 for speciation (24 Cryptosporidium hominis and 18 C. parvum). Children with C. hominis shed significantly more oocysts/ml of stool (3.5 x 10(6) vs. 1.7 x 10(6)perml; P=0.001), and oocyst counts were higher among symptomatic children (P=0.002). Heavier C. parvum shedding was significantly associated with symptoms (P=0.004), and symptomatic C. parvum-infected children were significantly more likely than asymptomatic children to be lactoferrin-positive (P=0.004). Height-for-age (HAZ) Z-scores showed significant declines within 3 months of infection for children infected with either C. hominis (P=0.028) or C. parvum (P=0.001). However, in the 3-6 month period following infection, only C. hominis-infected children continued to demonstrate declining HAZ score and asymptomatic children showed even greater decline (P=0.01). Cryptosporidium hominis is more common than C. parvum in favela children and is associated with heavier infections and greater growth shortfalls, even in the absence of symptoms.

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.To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa.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.

Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can also occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.This report covers cases with onset of illness in 2003, and summarizes trends over previous years.Malaria cases confirmed by blood film are mandated to be reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report.CDC received reports of 1,278 cases of malaria with an onset of symptoms in 2003, including seven fatal cases, among persons in the United States or one of its territories. This number represents a decrease of 4.4% from the 1,337 cases reported for 2002. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 53.3%, 22.9%, 3.6%, and 2.6% of cases, respectively. Twelve patients (0.9% of total) were infected by two or more species. The infecting species was unreported or undetermined in 212 (16.6%) cases. Compared with 2002, the number of reported malaria cases acquired in Asia (n = 177) and the Americas (n = 147) increased by 3.5% and 4.3% respectively, whereas the number of cases acquired in Africa (n = 840) decreased by 7.0%. Of 762 U.S. civilians who acquired malaria abroad, 132 (17.3%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Ten patients became infected in the United States, including one probable transfusion-related, one in which epidemiologic investigations failed to identify any apparent mode of acquisition, and eight which were introduced cases as a result of local mosquitoborne transmission. Of the seven deaths attributed to malaria, five were caused by P. falciparum, and a species was not identified in the other two.The 4.4% decrease in malaria cases in 2003, compared with 2002, resulted primarily from a decrease in cases acquired in Africa, but this decrease was offset by an increase in the number of cases acquired in the Americas and Asia. This small decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, or fluctuation in reporting to state and local health departments. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria.Additional information was obtained concerning the seven fatal cases and the 10 infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently experiences a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel. Recommendations concerning diagnosis of malaria and its treatment can be obtained by calling the Malaria Hotline or accessing CDC's Internet site at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm.

In sub-Saharan Africa, human immunodeficiency virus (HIV) and malaria are among the leading causes of morbidity during pregnancy. We reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia. Results from 11 studies showed that HIV-infected women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae. Thus, HIV alters the typical gravidity-specific pattern of malaria risk by shifting the burden from primarily primigravidae and secundigravidae to all pregnant women. The proportional increase of malaria during pregnancy attributable to HIV was estimated to be 5.5% and 18.8% for populations with HIV prevalences of 10% and 40%, respectively. Maternal malaria was associated with a two-fold higher HIV-1 viral concentrations. Three studies investigating whether placental malaria increased mother-to-child HIV-1 transmission showed conflicting results, possibly reflecting a complex balance between placental malarial immune responses and stimulation of HIV-1 viral replication. Further investigations of interactions between antiretroviral drugs, prophylaxis with cotrimoxazole, and antimalarial drugs in pregnant women are urgently needed. Although much has been learned in the past 15 years about the interaction between malaria and HIV-1 during pregnancy, many issues still require further information to improve our understanding. There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women.

Plasmodium falciparum infection during pregnancy may cause placental malaria and subsequently low birth weight, primarily through the placental sequestration of infected red blood cells. Measuring the burden of malaria during pregnancy usually involves determining the prevalence of placental malaria infection through microscopic examination of placental blood films, a difficult and error-prone process. A number of rapid diagnostic tests (RDTs) for malaria have been developed, most of them immunochromatographic dipstick assays. However, none have been tested for the direct determination of malaria antigen in placental blood. We undertook an evaluation of the Malaria Rapid Test (MAKROmed in determining placental malaria infection. The prevalence of placental parasitemia was 22.6% by microscopy, 51.0% by a polymerase chain reaction (PCR), and 43.1% by RDT. When the PCR was used as the gold standard, RDTs had a sensitivity of 89% and a specificity of 76%. The MAKROmed RDT was highly sensitive in the detection of placental malaria, but had lower than expected specificity.

Malaria is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.This report covers cases with onset of illness in 2001.Malaria cases confirmed by blood film are reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report.CDC received reports of 1,383 cases of malaria with an onset of symptoms in 2001 among persons in the United States or one of its territories. This number represents a decrease of 1.4% from the 1,402 cases reported for 2000. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 50.1%, 27.8%, 4.5%, and 3.6% of cases, respectively. Fourteen patients (1.0% of total) were infected by/=2 species. The infecting species was unreported or undetermined in 179 (12.9%) cases. Compared with 2000, the number of reported malaria cases acquired in Africa increased by 13.2% (n = 886), whereas the number of cases acquired in Asia (n = 163) and the Americas (n = 240) decreased by 31.5% and 11.4%, respectively. Of 891 U.S. civilians who acquired malaria abroad, 180 (20.2%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Two patients became infected in the United States, one through congenital transmission and one whose infection cannot be linked epidemiologically to secondary cases. Eleven deaths were attributed to malaria, 10 caused by P. falciparum and one caused by P. ovale.The 1.4% decrease in malaria cases in 2001, compared with 2000, resulted primarily from a decrease in cases acquired in Asia and the Americas, but this decrease was offset by an increase in the number of cases acquired in Africa. This decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, fluctuation in reporting to state and local health departments, or an increased use of effective antimalarial chemoprophylaxis. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria.Additional information was obtained concerning the 11 fatal cases and the two infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel.

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 Koupela 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 che- moprophylaxis 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.

Malaria is caused by four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). Malaria is transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur in persons who have traveled to areas with ongoing transmission. In the United States, cases can occur through exposure to infected blood products, by congenital transmission, or locally through mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers.Cases with onset of illness during 1999.Malaria cases confirmed by blood films are reported to local and state health departments by health-care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this report.CDC received reports of 1,540 cases of malaria with an onset of symptoms during 1999 among persons in the United States or one of its territories. This number represents an increase of 25.5% from the 1,227 cases reported for 1998. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 46.0%, 30.7%, 4.6%, and 3.6% of cases, respectively. More than one species was present in 12 patients (0.8% of total). The infecting species was unreported or undetermined in 223 (14.5%) cases. The number of reported malaria cases acquired in Africa increased 27.6% (n = 901), compared with 1998, and an increase of 2.9% (n = 246) occurred in cases acquired in Asia, compared with 1998. Cases from the Americas increased by 19.7% (n = 274) from 1998. Of 831 U.S. civilians who acquired malaria abroad, 159 (19.1%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Three patients became infected in the United States, all through probable local mosquitoborne transmission. Five deaths were attributed to malaria, all caused by P. falciparum.The 25.5% increase in malaria cases in 1999, compared with 1998, resulted primarily from increases in cases acquired in Africa and the Americas. This increase is possibly related to a change in the system by which states report to CDC, but it could also have resulted from local changes in disease transmission, increased travel to these regions, improved reporting to state and local health departments, or a decreased use of effective antimalarial chemoprophylaxis. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country where they acquired malaria.Additional information was obtained concerning the five fatal cases and the three infections acquired in the United States. The NMSS surveillance form was modified to gather more detailed information regarding compliance with prescribed chemoprophylaxis regimens. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate to the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning prevention of malaria can be obtained from CDC.

Little is known about the epidemiology of malaria during pregnancy in areas of unstable (epidemic-prone) transmission (UT) in sub-Saharan Africa. In cross-sectional studies peripheral malaria parasitemia was identified in 10.4% of women attending antenatal care clinics at 1 stable transmission (ST) site and in 1.8% of women at 3 UT sites; parasitemia was associated with anemia in both ST (relative risk [RR] 2.0; P < .001) and UT (RR 4.4; P < .001) sites. Placental parasitemia was identified more frequently during deliveries at ST sites (12/185; 6.5%) than at UT sites (21/833; 2.5%; P=.006). Placental parasitemia was associated with low birth weight at the ST site (RR 3.2; P=.01) and prematurity at ST (RR 2.7; P=.04) and UT (RR 3.9; P=.01) sites and with a 7-fold increased risk of stillbirths at UT sites. The effectiveness and efficiency in Ethiopia of standard preventive strategies used in high-transmission regions (such as intermittent preventive treatment) may require further evaluation; approaches such as insecticide-treated bednets and epidemic preparedness may be needed to prevent adverse pregnancy outcomes. (authors)