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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.

Summary objectives To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. methods Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6‐59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. results The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrolment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. conclusion Although artemether-lumefantrine (Coartem � ) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an

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

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.

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.

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. The objective was 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. (authors)

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

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.

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 ex- amination 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.

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.

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.

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.

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)

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.

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.

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.

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.

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.

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.

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)

This cohort study on Cryptosporidium infection was conducted among children born in an urban slum in northeastern Brazil. The study aimed to: elucidate the epidemiology of Cryptosporidium infection in an endemic setting; describe factors associated with Cryptosporidium-associated persistent diarrhea; and clarify the importance of copathogens in symptomatic cryptosporidiosis. Samples included an urban slum community of 2000 inhabitants near the medical campus of the Federal University of Ceara Fortaleza Brazil. Results showed a total of 1476 episodes of diarrhea accounting for 7581 days of illness; of these 102 episodes were persistent. Cryptosporidium oocysts were identified in 7.4% of all stools and they were found more frequently in children with persistent diarrhea than those with acute or no diarrhea. Results indicate that low-birth-weight children and those living in densely crowded subdivisions were at greater risks for symptomatic infection. Moreover the disease course was highly variable and was not associated with the presence of copathogens. Recurrent Cryptosporidium infection and the relapsing diarrhea associated with it were moderately common. Thus the WHO diarrheal definitions to Cryptosporidium-associated diarrheal episodes may need to be reconsidered.

To evaluate the impact of Cryptosporidium infection on diarrheal disease burden and nutrition status, a nested case-control study was done among children who were followed from birth in Fortaleza, Brazil. The diarrhea history and growth records of 43 children with a symptomatic diarrhea episode of cryptosporidiosis (case-children) were compared with those of 43 age-matched controls with no history of cryptosporidiosis. After Cryptosporidium infection, case-children < or = 1 year old experienced an excessive and protracted (nearly 2 years) diarrheal disease burden. Case-children < or = 1 year old with no history of diarrhea prior to their Cryptosporidium infection also experienced a subsequent increased diarrheal disease burden with an associated decline in growth. Control subjects experienced no change in their diarrhea burden over time. This study suggests that an episode of symptomatic Cryptosporidium infection in children < or = 1 year of age is a marker for increased diarrhea morbidity.

This abstract is submitted as part of the panel session on case studies for elimination by the WHO Global Malaria Programme and the UCSF Global Health Group.

Malaria during pregnancy is a major public health problem in sub-Saharan Africa and is associated with maternal anemia, low birth weight, and premature delivery. Efficacious prevention measures exist, namely, insecticide treated bednets and intermittent preventive treatment. Malaria remains a disease of poverty; the fact that poor women are also less likely to revive antenatal care worsens the opportunities for intervention for the most vulnerable women. Future research needs to focus on new drugs and drug combinations for use in pregnancy, the impact of combined use of insecticide-treated bednets and intermittent preventive treatment, and the further exploration of a pregnancy-specific malaria vaccine.

Background This case study examines the history of malaria in Cape Verde and presents details of the interventions implemented over the last 60 years with the aim of disease elimination. Trends in the malaria situation and programme policies and operations over time were evaluated and lessons captured to assist other countries in making wellinformed decisions regarding malaria elimination. The case study is a part of a joint series of malaria elimination case studies conducted by the WHO Global Malaria Programme and the University of California, San Francisco, Global Health Group.

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.