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Background: Community-based service delivery is vital to the effectiveness, affordability and sustainability of vector control generally, and to labour-intensive larval source management (LSM) programmes in particular., Case Description: The institutional evolution of a city-level, community-based LSM programme over 14 years in urban Dar es Salaam, Tanzania, illustrates how operational research projects can contribute to public health governance and to the establishment of sustainable service delivery programmes. Implementation, management and governance of this LSM programme is framed within a nested set of spatially-defined relationships between mosquitoes, residents, government and research institutions that build upward from neighbourhood to city and national scales., Discussion and Evaluation: The clear hierarchical structure associated with vertical, centralized management of decentralized, community-based service delivery, as well as increasingly clear differentiation of partner roles and responsibilities across several spatial scales, contributed to the evolution and subsequent growth of the programme., Conclusions: The UMCP was based on the principle of an integrated operational research project that evolved over time as the City Council gradually took more responsibility for management. The central role of Dar es Salaam's City Council in coordinating LSM implementation enabled that flexibility; the institutionalization of management and planning in local administrative structures enhanced community-mobilization and funding possibilities at national and international levels. Ultimately, the high degree of program ownership by the City Council and three municipalities, coupled with catalytic donor funding and technical support from expert overseas partners have enabled establishment of a sustainable, internally-funded programme implemented by the National Ministry of Health and Social Welfare and supported by national research and training institutes.

Background: Between 1997 and 2009, a number of key malaria control interventions were implemented in the Kilombero and Ulanga Districts in south central Tanzania to increase insecticide-treated nets (ITN) coverage and improve access to effective malaria treatment. In this study we estimated the contribution of these interventions to observed decreases in child mortality., Methods: The local Health and Demographic Surveillance Site (HDSS) provided monthly estimates of child mortality rates (age 1 to 5 years) expressed as cases per 1000 person-years (c/1000py) between 1997 and 2009. We conducted a time series analysis of child mortality rates and explored the contribution of rainfall and household food security. We used Poisson regression with linear and segmented effects to explore the impact of malaria control interventions on mortality., Results: Child mortality rates decreased by 42.5% from 14.6 c/1000py in 1997 to 8.4 c/1000py in 2009. Analyses revealed the complexity of child mortality patterns and a strong association with rainfall and food security. All malaria control interventions were associated with decreases in child mortality, accounting for the effect of rainfall and food security., Conclusions: Reaching the fourth Millenium Development Goal will require the contribution of many health interventions, as well as more general improvements in socio-environmental and nutritional conditions. Distinguishing between the effects of these multiple factors is difficult and represents a major challenge in assessing the effect of routine interventions. However, this study suggests that credible estimates can be obtained when high-quality data on the most important factors are available over a sufficiently long time period.

Background: Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance., Methods: Twenty-four areas were randomly assigned to receive or not receive IPTi. Blood collected during representative household surveys at baseline and 15 and 27 months after implementation was tested for SP and resistance markers., Results: The frequency of SP in blood was similar in the IPTi and comparison areas at baseline and at 15 months. dhfr and dhps mutations were also similar at baseline and then increased similarly in both arms after 15 months of SP-IPTi. First-line treatment was switched from SP to artemether-lumefantrine before the final survey, when SP positivity fell among infants in comparison areas but increased in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations in IPTi areas (P = .004 and P = .18, respectively)., Conclusions: IPTi did not increase drug pressure or the selection on dhfr and dhps mutants, when SP was the first-line malaria treatment. Introduction of artemether-lumefantrine was followed by an increase in dhfr mutations, consistent with weak selection attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a fitness cost of this mutation.

Background: The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up., Methods: This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20., Results: From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545)., Conclusions: The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population., Clinical Trials: Gov identifier: NCT00289185.

Background: Intermittent preventive treatment of malaria in infants (IPTi) consists of the administration of a treatment dose of sulphadoxine-pyrimethamine (SP) at the time of routine vaccinations. The use of routine Health Management and Information Services (HMIS) data to investigate the effect of IPTi on malaria, anaemia, and all-cause attendance in children aged 2-11 months presenting to 11 health centres in southern Tanzania is described., Methods: Clinical diagnosis of malaria was confirmed with a positive blood slide reading from a quality assurance laboratory. Anaemia was defined using two thresholds (mild [Hb<11 g/dL], severe [Hb<8 g/dL]). Incidence rates between IPTi and non-implementing health centres were calculated using Poisson regression, and all statistical testing was based on the t test due to the clustered nature of the data., Results: Seventy two per cent of infants presenting in intervention areas received at least one dose of IPTi--22% received all three. During March 2006-April 2007, the incidence of all cause attendance was two attendances per person, per year (pppy), including 0.2 episodes pppy of malaria, 0.7 episodes of mild and 0.13 episodes of severe anaemia. Point estimates for the effect of IPTi on malaria varied between 18% and 52%, depending on the scope of the analysis, although adjustment for clustering rendered these not statistically significant., Conclusions: The point estimate of the effect of IPTi on malaria is consistent with that from a large pooled analysis of randomized control trials. As such, it is plausible that the difference seen in health centre data is due to IPTi, even thought the effect did not reach statistical significance. Findings draw attention to the challenges of robust inference of effects of interventions based on routine health centre data. Analysis of routine health information can reassure that interventions are being made available and having desired effects, but unanticipated effects should trigger data collection from representative samples of the target population.

Background: Across sub-Saharan Africa, pregnant women attend routine health services around the 20th week of gestation., Objective: To investigate, with a view to maximising effectiveness of malaria control tools delivered via routine services, coverage of an antenatal clinic insecticide-treated net (ITN) voucher scheme in Tanzania by gestational age., Methods: Household and antenatal clinic survey data from 21 districts in Tanzania were collected and analysed annually 2005-2007. Optimal voucher protection was defined as giving women access to vouchers for 24 weeks of pregnancy (weeks 16 and 40 gestation). The relationship between gestational age and use of ITNs throughout pregnancy was explored., Results: Coverage of the ITN voucher was high (84% in 2007), but only 61% of optimal voucher protection was achieved. It was reduced by a combination of late attendance at clinic and staff not distributing vouchers at first visit. An increasing trend by gestational age in ITN use was observed each survey year, rising in 2007 from 23% of first-trimester women to 30% of women post partum (χ(2)=5.9, p=0.01)., Conclusion: Uptake of malaria interventions is not evenly distributed throughout pregnancy. Including gestational age in pregnancy coverage indicators can enhance understanding of the public health potential available from pregnancy interventions.

Background: To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania., Methods: The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS) and in Ifakara town. Data collection consisted of: 1) yearly censuses of shops selling drugs; 2) collection of monthly data on availability of anti-malarials in public health facilities; and 3) retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data., Results: Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008) and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008) of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock), but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock), but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial sales), Conclusions: The public health and private retail sector are important complementary sources of treatment in rural Tanzania. Ensuring the availability of ALu in the private retail sector is important for its successful uptake.

Background: The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment., Methods: Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS) and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days., Results: Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%); an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%); higher treatment coverage with anti-malarials (86% to 96%) and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs). Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%). The availability of outlets (health facilities or drug shops) is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent., Conclusions: An integrated approach aimed at improving understanding and treatment of malaria has led to tangible improvements in terms of people's actions for the treatment of malaria. However, progress was hindered by the low availability of the first-line treatment after the switch to ACT.

Intermittent preventive treatment of malaria in infants (IPTi) with sulphadoxine-pyrimethamine shows evidence of efficacy in individually randomized, controlled trials. In a large-scale effectiveness study, IPTi was introduced in April 2005 by existing health staff through routine contacts in 12 randomly selected divisions out of 24 in 6 districts of rural southern Tanzania. Coverage and effects on malaria and anemia were estimated through a representative survey in 2006 with 600 children aged 2-11 months. Coverage of IPTi was 47-76% depending on the definition. Using an intention to treat analysis, parasitemia prevalence was 31% in intervention and 38% in comparison areas (P = 0.06). In a "per protocol" analysis of children who had recently received IPTi, parasite prevalence was 22%, 19 percentage points lower than comparison children (P = 0.01). IPTi can be implemented on a large scale by existing health service staff, with a measurable population effect on malaria, within 1 year of launch.

Objectives: To evaluate the impact of the Tanzania National Voucher Scheme on the coverage and equitable distribution of insecticide treated nets, used to prevent malaria, to pregnant women and their infants., Design: Plausibility study using three nationally representative cross sectional household and health facility surveys, timed to take place early, mid-way, and at the end of the roll out of the national programme., Setting: The Tanzania National Voucher Scheme was implemented in antenatal services, and phased in on a district by district basis from October 2004 covering all of mainland Tanzania in May 2006., Participants: 6115, 6260, and 6198 households (in 2005, 2006, and 2007, respectively) in a representative sample of 21 districts (out of a total of 113)., Interventions: A voucher worth $2.45 ( pound1.47, euro1.74) to be used as part payment for the purchase of a net from a local shop was given to every pregnant woman attending antenatal services., Main Outcome Measures: Insecticide treated net coverage was measured as household ownership of at least one net and use of a net the night before the survey. Socioeconomic distribution of nets was examined using an asset based index., Results: Steady increases in net coverage indicators were observed over the three year study period. Between 2005 and 2007, household ownership of at least one net (untreated or insecticide treated) increased from 44% (2686/6115) to 65% (4006/6198; P<0.001), and ownership of at least one insecticide treated net doubled from 18% (1062/5961) to 36% (2229/6198) in the same period (P<0.001). Among infants under 1 year of age, use of any net increased from 33% (388/1180) to 56% (707/1272; P<0.001) and use of an insecticide treated net increased from 16% (188/1180) to 34% (436/1272; P<0.001). After adjusting for potential confounders, household ownership was positively associated with time since programme launch, although this association did not reach statistical significance (P=0.09). Each extra year of programme operation was associated with a 9 percentage point increase in household insecticide treated net ownership (95% confidence interval -1.6 to 20). In 2005, only 7% (78/1115) of nets in households with a child under 1 year of age had been purchased with a voucher; this value increased to 50% (608/1211) in 2007 (P<0.001). In 2007, infants under 1 year in the least poor quintile were more than three times more likely to have used an insecticide treated net than infants in the poorest quintile (54% v 16%; P<0.001)., Conclusions: The Tanzania National Voucher Scheme was associated with impressive increases in the coverage of insecticide treated nets over a two year period. Gaps in coverage remain, however, especially in the poorest groups. A voucher system that facilitates routine delivery of insecticide treated nets is a feasible option to "keep up" coverage.

Background to the Debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five.

Background: Malaria control in Africa is most tractable in urban settlements yet most research has focused on rural settings. Elimination of malaria transmission from urban areas may require larval control strategies that complement adult mosquito control using insecticide-treated nets or houses, particularly where vectors feed outdoors., Methods and Findings: Microbial larvicide (Bacillus thuringiensis var. israelensis (Bti)) was applied weekly through programmatic, non-randomized community-based, but vertically managed, delivery systems in urban Dar es Salaam, Tanzania. Continuous, randomized cluster sampling of malaria infection prevalence and non-random programmatic surveillance of entomological inoculation rate (EIR) respectively constituted the primary and secondary outcomes surveyed within a population of approximately 612,000 residents in 15 fully urban wards covering 55 km(2). Bti application for one year in 3 of those wards (17 km(2) with 128,000 residents) reduced crude annual transmission estimates (Relative EIR [95% Confidence Interval] = 0.683 [0.491-0.952], P = 0.024) but program effectiveness peaked between July and September (Relative EIR [CI] = 0.354 [0.193 to 0.650], P = 0.001) when 45% (9/20) of directly observed transmission events occurred. Larviciding reduced malaria infection risk among children < or =5 years of age (OR [CI] = 0.284 [0.101 to 0.801], P = 0.017) and provided protection at least as good as personal use of an insecticide treated net (OR [CI] = 0.764 [0.614-0.951], P = 0.016)., Conclusions: In this context, larviciding reduced malaria prevalence and complemented existing protection provided by insecticide-treated nets. Larviciding may represent a useful option for integrated vector management in Africa, particularly in its rapidly growing urban centres.

Minimizing the time between efficacy studies and public health action is important to maximize health gains. We report the rationale, development and implementation of a district-based strategy for the implementation of intermittent preventive treatment in infants (IPTi) for malaria and anaemia control in Tanzania. From the outset, a research team worked with staff from all levels of the health system to develop a public-health strategy that could continue to function once the research team withdrew. The IPTi strategy was then implemented by routine health services to ensure that IPTi behaviour-change communication materials were available in health facilities, that health workers were trained to administer and to document doses of IPTi, that the necessary drugs were available in facilities and that systems were in place for stock management and supervision. The strategy was integrated into existing systems as far as possible and well accepted by health staff. Time-and-motion studies documented that IPTi implementation took a median of 12.4 min (range 1.6-28.9) per nurse per vaccination clinic. The collaborative approach between researchers and health staff effectively translated research findings into a strategy fit for public health implementation.

Background: Delivery of two doses of intermittent preventive treatment of malaria during pregnancy (IPTp) is a key strategy to reduce the burden of malaria in pregnancy in sub-Saharan Africa. However, different settings have reported coverage levels well below the target 80%. Antenatal implementation guidelines in Tanzania recommend IPTp first dose to be given at the second antenatal visit, and second dose at the third visit. This investigation measured coverage of IPTp at national level in Tanzania and examined the role of individual, facility, and policy level influences on achieved coverage., Methods: Three national household and linked reproductive and child health (RCH) facility surveys were conducted July-August 2005, 2006, and 2007 in 210 clusters sampled using two-stage cluster sampling from 21 randomly selected districts. Female residents who reported a livebirth in the previous year were asked questions about malaria prevention during that pregnancy and individual characteristics including education, pregnancy history, and marital status. The RCH facility serving each cluster was also surveyed, and information collected about drug stocks, health education delivery, and the timing of antenatal care delivery by clinic users., Results: The national IPTp coverage had declined over the survey period being 71% for first dose in 2005 falling to 65% in 2007 (chi2 2.9, p = 0.05), and 38% for second dose in 2005 but 30% in 2007 (chi2 4.4, p = 0.01). There was no evidence of any individual factors being associated with second dose coverage beyond living in an urban area. Availability of sulphadoxine-pyrimethamine at RCH had decreased year on year from 85% of clinics in stock in 2005 to 60% in 2007 (chi2 20.6, p < 0.001). This reduction was evident in rural but not urban clinics. If safety recommendations and national antenatal care guidelines for IPTp delivery were followed, in 2007 only 76% of pregnant women could have received IPTp first dose and only 46% could have received second dose., Conclusion: There is scope to improve IPTp first and second dose coverage at national scale within existing systems by improving stock at RCH, and by revising the existing guidelines to recommend delivery of IPTp after quickening, rather than at a pre-defined antenatal visit.

Background: Intermittent preventive treatment of malaria in infants (IPTi) reduces the incidence of clinical malaria. However, before making decisions about implementation, it is essential to ensure that IPTi is acceptable, that it does not adversely affect attitudes to immunization or existing health seeking behaviour. This paper reports on the reception of IPTi during the first implementation study of IPTi in southern Tanzania., Methods: Data were collected through in-depth interviews, focus group discussions and participant observation carried out by a central team of social scientists and a network of key informants/interviewers who resided permanently in the study sites., Results: IPTi was generally acceptable. This was related to routinization of immunization and resonance with traditional practices. Promoting "health" was considered more important than preventing specific diseases. Many women thought that immunization was obligatory and that health staff might be unwilling to assist in the future if they were non-adherent. Weighing and socialising were important reasons for clinic attendance. Non-adherence was due largely to practical, social and structural factors, many of which could be overcome. Reasons for non-adherence were sometimes interlinked. Health staff and "road to child health" cards were the main source of information on the intervention, rather than the specially designed posters. Women did not generally discuss child health matters outside the clinic, and information about the intervention percolated slowly through the community. Although there were some rumours about sulphadoxine pyrimethamine (SP), it was generally acceptable as a drug for IPTi, although mothers did not like the way tablets were administered. There is no evidence that IPTi had a negative effect on attitudes or adherence to the expanded programme on immunisation (EPI) or treatment seeking or existing malaria prevention., Conclusion: In order to improve adherence to both EPI and IPTi local priorities should be taken into account. For example, local women are often more interested in weighing than in immunization, and they view vaccination and IPTi as vaguely "healthy" rather preventing specific diseases. There should be more emphasis on these factors and more critical consideration by policy makers of how much local knowledge and understanding is minimally necessary in order to make interventions successful.

Background: Intermittent preventive treatment of malaria in infants (IPTi) using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI) is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health strategy, information is needed so that this novel control tool can be put into practice promptly, once a policy recommendation is made to implement it. This paper describes the development of a behaviour change communication strategy to support implementation of IPTi by the routine health services in southern Tanzania, in the context of a five-year research programme evaluating the community effectiveness of IPTi., Methods: Mixed methods including a rapid qualitative assessment and quantitative health facility survey were used to investigate communities' and providers' knowledge and practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing health posters. Results were applied to develop an appropriate behaviour change communication strategy for IPTi involving personal communication between mothers and health staff, supported by a brand name and two posters., Results: Malaria in young children was considered to be a nuisance because it causes sleepless nights. Vaccination services were well accepted and their use was considered the mother's responsibility. Babies were generally taken for vaccination despite complaints about fevers and swellings after the injections. Sulphadoxine-pyrimethamine was widely used for malaria treatment and intermittent preventive treatment of malaria in pregnancy, despite widespread rumours of adverse reactions based on hearsay and newspaper reports. Almost all health providers said that they or their spouse were ready to take SP in pregnancy (96%, 223/242). A brand name, key messages and images were developed and pre-tested as behaviour change communication materials. The posters contained public health messages, which explained the intervention itself, how and when children receive it and safety issues. Implementation of IPTi started in January 2005 and evaluation is ongoing., Conclusion: Behaviour Change Communication (BCC) strategies for health interventions must be both culturally appropriate and technically sound. A mixed methods approach can facilitate an interactive process among relevant actors to develop a BCC strategy.

Background: Malaria is still a leading child killer in sub-Saharan Africa. Yet, access to prompt and effective malaria treatment, a mainstay of any malaria control strategy, is sub-optimal in many settings. Little is known about obstacles to treatment and community-effectiveness of case-management strategies. This research quantified treatment seeking behaviour and access to treatment in a highly endemic rural Tanzanian community. The aim was to provide a better understanding of obstacles to treatment access in order to develop practical and cost-effective interventions., Methods: We conducted community-based treatment-seeking surveys including 226 recent fever episodes in 2004 and 2005. The local Demographic Surveillance System provided additional household information. A census of drug retailers and health facilities provided data on availability and location of treatment sources., Results: After intensive health education, the biomedical concept of malaria has largely been adopted by the community. 87.5% (78.2-93.8) of the fever cases in children and 80.7% (68.1-90.0) in adults were treated with one of the recommended antimalarials (at the time SP, amodiaquine or quinine). However, only 22.5% (13.9-33.2) of the children and 10.5% (4.0-21.5) of the adults received prompt and appropriate antimalarial treatment. Health facility attendance increased the odds of receiving an antimalarial (OR = 7.7) but did not have an influence on correct dosage. The exemption system for under-fives in public health facilities was not functioning and drug expenditures for children were as high in health facilities as with private retailers., Conclusion: A clear preference for modern medicine was reflected in the frequent use of antimalarials. Yet, quality of case-management was far from satisfactory as was the functioning of the exemption mechanism for the main risk group. Private drug retailers played a central role by complementing existing formal health services in delivering antimalarial treatment. Health system factors like these need to be tackled urgently in order to translate the high efficacy of newly introduced artemisinin-based combination therapy (ACT) into equitable community-effectiveness and health-impact.

Background: Medical entomologists increasingly recognize that the ability to make inferences between laboratory experiments of vector biology and epidemiological trends observed in the field is hindered by a conceptual and methodological gap occurring between these approaches which prevents hypothesis-driven empirical research from being conducted on relatively large and environmentally realistic scales. The development of Semi-Field Systems (SFS) has been proposed as the best mechanism for bridging this gap. Semi-field systems are defined as enclosed environments, ideally situated within the natural ecosystem of a target disease vector and exposed to ambient environmental conditions, in which all features necessary for its life cycle completion are present. Although the value of SFS as a research tool for malaria vector biology is gaining recognition, only a few such facilities exist worldwide and are relatively small in size (< 100 m2)., Methods: The establishment of a 625 m2 state-of-the-art SFS for large-scale experimentation on anopheline mosquito ecology and control within a rural area of southern Tanzania, where malaria transmission intensities are amongst the highest ever recorded, is described., Results: A greenhouse frame with walls of mosquito netting and a polyethylene roof was mounted on a raised concrete platform at the Ifakara Health Institute. The interior of the SFS was divided into four separate work areas that have been set up for a variety of research activities including mass-rearing for African malaria vectors under natural conditions, high throughput evaluation of novel mosquito control and trapping techniques, short-term assays of host-seeking behaviour and olfaction, and longer-term experimental investigation of anopheline population dynamics and gene flow within a contained environment that simulates a local village domestic setting., Conclusion: The SFS at Ifakara was completed and ready for use in under two years. Preliminary observations indicate that realistic and repeatable observations of anopheline behaviour are obtainable within the SFS, and that habitat and climatic features representative of field conditions can be simulated within it. As work begins in the SFS in Ifakara and others around the world, the major opportunities and challenges to the successful application of this tool for malaria vector research and control are discussed.

Background: Achieving the Millennium Development Goals for health requires a massive scaling-up of interventions in Sub Saharan Africa. Intermittent Preventive Treatment in infants (IPTi) is a promising new tool for malaria control. Although efficacy information is available for many interventions, there is a dearth of data on the resources required for scaling up of health interventions., Method: We worked in partnership with the Ministry of Health and Social Welfare (MoHSW) to develop an IPTi strategy that could be implemented and managed by routine health services. We tracked health system and other costs of (1) developing the strategy and (2) maintaining routine implementation of the strategy in five districts in southern Tanzania. Financial costs were extracted and summarized from a costing template and semi-structured interviews were conducted with key informants to record time and resources spent on IPTi activities., Results: The estimated financial cost to start-up and run IPTi in the whole of Tanzania in 2005 was US$1,486,284. Start-up costs of US$36,363 were incurred at the national level, mainly on the development of Behaviour Change Communication (BCC) materials, stakeholders' meetings and other consultations. The annual running cost at national level for intervention management and monitoring and drug purchase was estimated at US$459,096. Start-up costs at the district level were US$7,885 per district, mainly expenditure on training. Annual running costs were US$170 per district, mainly for printing of BCC materials. There was no incremental financial expenditure needed to deliver the intervention in health facilities as supplies were delivered alongside routine vaccinations and available health workers performed the activities without working overtime. The economic cost was estimated at 23 US cents per IPTi dose delivered., Conclusion: The costs presented here show the order of magnitude of expenditures needed to initiate and to implement IPTi at national scale in settings with high Expanded Programme on Immunization (EPI) coverage. The IPTi intervention appears to be affordable even within the budget constraints of Ministries of Health of most sub-Saharan African countries.

Background: Since 2000, the World Health Organization has recommended a package of interventions to prevent malaria during pregnancy and its sequelae that includes the promotion of insecticide-treated bed nets (ITNs), intermittent preventive treatment in pregnancy (IPTp), and effective case management of malarial illness. It is recommended that pregnant women in malaria-endemic areas receive at least two doses of sulphadoxine-pyrimethamine in the second and third trimesters of pregnancy. This study assessed the prevalence of placental malaria at delivery in women during 1st or 2nd pregnancy, who did not receive intermittent preventive treatment for malaria (IPTp) in a malaria-endemic area with high bed net coverage., Methods: A hospital-based cross-sectional study was done in Ifakara, Tanzania, where bed net coverage is high. Primi- and secundigravid women, who presented to the labour ward and who reported not using IPTp were included in the study. Self-report data were collected by questionnaire; whereas neonatal birth weight and placenta parasitaemia were measured directly at the time of delivery., Results: Overall, 413 pregnant women were enrolled of which 91% reported to have slept under a bed net at home the previous night, 43% reported history of fever and 62% were primigravid. Malaria parasites were detected in 8% of the placenta samples; the geometric mean (95%CI) placental parasite density was 3,457 (1,060-11,271) parasites/mul in primigravid women and 2,178 (881-5,383) parasites/mul in secundigravid women. Fifteen percent of newborns weighed <2,500 g at delivery. Self-reported bed net use was statistically associated with lower risk for low birth weight [OR 0.34 (95% CI: 0.16-0.74) and OR 0.22 (95% CI: 0.08-0.59) for untreated and treated bed nets, respectively], but was not associated with placental parasitaemia [OR 0.74 (0.21-2.68) and OR 1.64 (0.44-6.19) for untreated and treated bed nets, respectively]., Conclusion: The observed incidence of LBW and prevalence of placental parasitaemia at delivery suggests that malaria remains a problem in pregnancy in this area with high bed net coverage when eligible women do not receive IPTp. Delivery of IPTp should be emphasized at all levels of implementation to achieve maximum community coverage.

Background: The Tanzania National Voucher Scheme (TNVS) uses the public health system and the commercial sector to deliver subsidised insecticide-treated nets (ITNs) to pregnant women. The system began operation in October 2004 and by May 2006 was operating in all districts in the country. Evaluating complex public health interventions which operate at national level requires a multidisciplinary approach, novel methods, and collaboration with implementers to support the timely translation of findings into programme changes. This paper describes this novel approach to delivering ITNs and the design of the monitoring and evaluation (M&E)., Methods: A comprehensive and multidisciplinary M&E design was developed collaboratively between researchers and the National Malaria Control Programme. Five main domains of investigation were identified: (1) ITN coverage among target groups, (2) provision and use of reproductive and child health services, (3) "leakage" of vouchers, (4) the commercial ITN market, and (5) cost and cost-effectiveness of the scheme., Results: The evaluation plan combined quantitative (household and facility surveys, voucher tracking, retail census and cost analysis) and qualitative (focus groups and in-depth interviews) methods. This plan was defined in collaboration with implementing partners but undertaken independently. Findings were reported regularly to the national malaria control programme and partners, and used to modify the implementation strategy over time., Conclusion: The M&E of the TNVS is a potential model for generating information to guide national and international programmers about options for delivering priority interventions. It is independent, comprehensive, provides timely results, includes information on intermediate processes to allow implementation to be modified, measures leakage as well as coverage, and measures progress over time.

Background: Tanzania has a well-developed network of commercial ITN retailers. In 2004, the government introduced a voucher subsidy for pregnant women and, in mid 2005, helped distribute free nets to under-fives in small number of districts, including Rufiji on the southern coast, during a child health campaign. Contributions of these multiple insecticide-treated net delivery strategies existing at the same time and place to coverage in a poor rural community were assessed., Methods: Cross-sectional household survey in 6,331 members of randomly selected 1,752 households of 31 rural villages of Demographic Surveillance System in Rufiji district, Southern Tanzania was conducted in 2006. A questionnaire was administered to every consenting respondent about net use, treatment status and delivery mechanism., Findings: Net use was 62.7% overall, 87.2% amongst infants (0 to 1 year), 81.8% amongst young children (>1 to 5 years), 54.5% amongst older children (6 to 15 years) and 59.6% amongst adults (>15 years). 30.2% of all nets had been treated six months prior to interview. The biggest source of nets used by infants was purchase from the private sector with a voucher subsidy (41.8%). Half of nets used by young children (50.0%) and over a third of those used by older children (37.2%) were obtained free of charge through the vaccination campaign. The largest source of nets amongst the population overall was commercial purchase (45.1% use) and was the primary means for protecting adults (60.2% use). All delivery mechanisms, especially sale of nets at full market price, under-served the poorest but no difference in equity was observed between voucher-subsidized and freely distributed nets., Conclusion: All three delivery strategies enabled a poor rural community to achieve net coverage high enough to yield both personal and community level protection for the entire population. Each of them reached their relevant target group and free nets only temporarily suppressed the net market, illustrating that in this setting that these are complementary rather than mutually exclusive approaches.

Background: Throughout Africa, the private retail sector has been recognised as an important source of antimalarial treatment, complementing formal health services. However, the quality of advice and treatment at private outlets is a widespread concern, especially with the introduction of artemisinin-based combination therapies (ACTs). As a result, ACTs are often deployed exclusively through public health facilities, potentially leading to poorer access among parts of the population. This research aimed at assessing the performance of the retail sector in rural Tanzania. Such information is urgently required to improve and broaden delivery channels for life-saving drugs., Methods: During a comprehensive shop census in the districts of Kilombero and Ulanga, Tanzania, we interviewed 489 shopkeepers about their knowledge of malaria and malaria treatment. A complementary mystery shoppers study was conducted in 118 retail outlets in order to assess the vendors' drug selling practices. Both studies included drug stores as well as general shops., Results: Shopkeepers in drug stores were able to name more malaria symptoms and were more knowledgeable about malaria treatment than their peers in general shops. In drug stores, 52% mentioned the correct child-dosage of sulphadoxine-pyrimethamine (SP) compared to only 3% in general shops. In drug stores, mystery shoppers were more likely to receive an appropriate treatment (OR = 9.6), but at an approximately seven times higher price. Overall, adults were more often sold an antimalarial than children (OR = 11.3). On the other hand, general shopkeepers were often ready to refer especially children to a higher level if they felt unable to manage the case., Conclusion: The quality of malaria case-management in the retail sector is not satisfactory. Drug stores should be supported and empowered to provide correct malaria-treatment with drugs they are allowed to dispense. At the same time, the role of general shops as first contact points for malaria patients needs to be re-considered. Interventions to improve availability of ACTs in the retail sector are urgently required within the given legal framework.

Background: As the population of Africa rapidly urbanizes, large populations could be protected from malaria by controlling aquatic stages of mosquitoes if cost-effective and scalable implementation systems can be designed., Methods: A recently initiated Urban Malaria Control Programme in Dar es Salaam delegates responsibility for routine mosquito control and surveillance to modestly-paid community members, known as Community-Owned Resource Persons (CORPs). New vector surveillance, larviciding and management systems were designed and evaluated in 15 city wards to allow timely collection, interpretation and reaction to entomologic monitoring data using practical procedures that rely on minimal technology. After one year of baseline data collection, operational larviciding with Bacillus thuringiensis var. israelensis commenced in March 2006 in three selected wards., Results: The procedures and staff management systems described greatly improved standards of larval surveillance relative to that reported at the outset of this programme. In the first year of the programme, over 65,000 potential Anopheles habitats were surveyed by 90 CORPs on a weekly basis. Reaction times to vector surveillance at observations were one day, week and month at ward, municipal and city levels, respectively. One year of community-based larviciding reduced transmission by the primary malaria vector, Anopheles gambiae s.l., by 31% (95% C.I. = 21.6-37.6%; p = 0.04)., Conclusion: This novel management, monitoring and evaluation system for implementing routine larviciding of malaria vectors in African cities has shown considerable potential for sustained, rapidly responsive, data-driven and affordable application. Nevertheless, the true programmatic value of larviciding in urban Africa can only be established through longer-term programmes which are stably financed and allow the operational teams and management infrastructures to mature by learning from experience.

Background: The Kilombero Valley is a highly malaria-endemic agricultural area in south-eastern Tanzania. Seasonal flooding of the valley is favourable to malaria transmission. During the farming season, many households move to distant field sites (shamba in Swahili) in the fertile river floodplain for the cultivation of rice. In the shamba, people live for several months in temporary shelters, far from the nearest health services. This study assessed the impact of seasonal movements to remote fields on malaria risk and treatment-seeking behaviour., Methods: A longitudinal study followed approximately 100 randomly selected farming households over six months. Every household was visited monthly and whereabouts of household members, activities in the fields, fever cases and treatment seeking for recent fever episodes were recorded., Results: Fever incidence rates were lower in the shamba compared to the villages and moving to the shamba did not increase the risk of having a fever episode. Children aged 1-4 years, who usually spend a considerable amount of time in the shamba with their caretakers, were more likely to have a fever than adults (odds ratio = 4.47, 95% confidence interval 2.35-8.51). Protection with mosquito nets in the fields was extremely good (98% usage) but home-stocking of antimalarials was uncommon. Despite the long distances to health services, 55.8% (37.9-72.8) of the fever episodes were treated at a health facility, while home-management was less common (37%, 17.4-50.5)., Conclusion: Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods.

Background: Intermittent preventive treatment (IPTi) with sulphadoxine-pyrimethamine (SP) in infants resulted in different estimates of clinical malaria protection in two trials that used the same protocol in Ifakara, Tanzania, and Manhiça, Mozambique. Understanding the reasons for the discrepant results will help to elucidate the action mechanism of this intervention, which is essential for rational policy formulation., Methods: A comparative analysis of two IPTi trials that used the same study design, follow-up, intervention, procedures and assessment of outcomes, in Tanzania and Mozambique was undertaken. Children were randomised to receive either SP or placebo administered 3 times alongside routine vaccinations delivered through the Expanded Program on Immunisation (EPI). Characteristics of the two areas and efficacy on clinical malaria after each dose were compared., Results: The most relevant difference was in ITN's use ; 68% in Ifakara and zero in Manhiça. In Ifakara, IPTi was associated with a 53% (95% CI 14.0; 74.1) reduction in the risk of clinical malaria between the second and the third dose; during the same period there was no significant effect in Manhiça. Similarly, protection against malaria episodes was maintained in Ifakara during 6 months after dose 3, but no effect of IPTi was observed in Manhiça., Conclusion: The high ITN coverage in Ifakara is the most likely explanation for the difference in IPTi efficacy on clinical malaria. Combination of IPTi and ITNs may be the most cost-effective tool for malaria control currently available, and needs to be explored in current and future studies., Trial Registration: Manhiça study registration number: NCT00209795Ifakara study registration number: NCT88523834.

Background: Successful malaria vector control depends on understanding behavioural interactions between mosquitoes and humans, which are highly setting-specific and may have characteristic features in urban environments. Here mosquito biting patterns in Dar es Salaam, Tanzania are examined and the protection against exposure to malaria transmission that is afforded to residents by using an insecticide-treated net (ITN) is estimated., Methods: Mosquito biting activity over the course of the night was estimated by human landing catch in 216 houses and 1,064 residents were interviewed to determine usage of protection measures and the proportion of each hour of the night spent sleeping indoors, awake indoors, and outdoors., Results: Hourly variations in biting activity by members of the Anopheles gambiae complex were consistent with classical reports but the proportion of these vectors caught outdoors in Dar es Salaam was almost double that of rural Tanzania. Overall, ITNs confer less protection against exophagic vectors in Dar es Salaam than in rural southern Tanzania (59% versus 70%). More alarmingly, a biting activity maximum that precedes 10 pm and much lower levels of ITN protection against exposure (38%) were observed for Anopheles arabiensis, a vector of modest importance locally, but which predominates transmission in large parts of Africa., Conclusion: In a situation of changing mosquito and human behaviour, ITNs may confer lower, but still useful, levels of personal protection which can be complemented by communal transmission suppression at high coverage. Mosquito-proofing houses appeared to be the intervention of choice amongst residents and further options for preventing outdoor transmission include larviciding and environmental management.

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

Background: Prompt access to effective treatment is central in the fight against malaria. However, a variety of interlinked factors at household and health system level influence access to timely and appropriate treatment and care. Furthermore, access may be influenced by global and national health policies. As a consequence, many malaria episodes in highly endemic countries are not treated appropriately., Project: The ACCESS Programme aims at understanding and improving access to prompt and effective malaria treatment and care in a rural Tanzanian setting. The programme's strategy is based on a set of integrated interventions, including social marketing for improved care seeking at community level as well as strengthening of quality of care at health facilities. This is complemented by a project that aims to improve the performance of drug stores. The interventions are accompanied by a comprehensive set of monitoring and evaluation activities measuring the programme's performance and (health) impact. Baseline data demonstrated heterogeneity in the availability of malaria treatment, unavailability of medicines and treatment providers in certain areas as well as quality problems with regard to drugs and services., Conclusion: The ACCESS Programme is a combination of multiple complementary interventions with a strong evaluation component. With this approach, ACCESS aims to contribute to the development of a more comprehensive access framework and to inform and support public health professionals and policy-makers in the delivery of improved health services.

Background: Integrated vector management (IVM) for malaria control requires ecological skills that are very scarce and rarely applied in Africa today. Partnerships between communities and academic ecologists can address this capacity deficit, modernize the evidence base for such approaches and enable future scale up., Methods: Community-based IVM programmes were initiated in two contrasting settings. On Rusinga Island, Western Kenya, community outreach to a marginalized rural community was achieved by University of Nairobi through a community-based organization. In Dar es Salaam, Tanzania, Ilala Municipality established an IVM programme at grassroots level, which was subsequently upgraded and expanded into a pilot scale Urban Malaria Control Programme with support from national academic institutes., Results: Both programmes now access relevant expertise, funding and policy makers while the academic partners benefit from direct experience of community-based implementation and operational research opportunities. The communities now access up-to-date malaria-related knowledge and skills for translation into local action. Similarly, the academic partners have acquired better understanding of community needs and how to address them., Conclusion: Until sufficient evidence is provided, community-based IVM remains an operational research activity. Researchers can never directly support every community in Africa so community-based IVM strategies and tactics will need to be incorporated into undergraduate teaching programmes to generate sufficient numbers of practitioners for national scale programmes. Academic ecologists at African institutions are uniquely positioned to enable the application of practical environmental and entomological skills for malaria control by communities at grassroots level and should be supported to fulfil this neglected role.

Treated mosquito nets are a practical malaria control tool. However, implementation of efficient delivery mechanisms remains a challenge. We investigated whether social marketing of treated mosquito nets results in decreased equity in rural Tanzania, through household surveys before the start of a social marketing programme and 3 years later. About 12,000 household heads were asked about ownership of nets and other assets including a tin roof, radio, or bicycle. A socio-economic status score was developed for each household. Net ownership was calculated for households in each quintile of this score, from poorest to least poor. In 1997, about 20% of the poorest households and over 60% of the least poor households owned a mosquito net. Three years later, more than half of the poorest households owned a net, as did over 90% of the least poor: the ratio of net ownership among the poorest to least poor increased from 0.3 in 1997 to 0.6 in 2000. Social marketing in the presence of an active private sector for nets was associated with increased equity.

Background: Insecticide-treated nets represent currently a key malaria control strategy, but low insecticide re-treatment rates remain problematic. Olyset nets are currently one of two long-lasting insecticidal nets recommended by WHO. An assessment was carried out of the effect of Olyset nets after seven years of use in rural Tanzania., Methods: A survey of Olyset nets was conducted in two Tanzanian villages to examine their insecticide dosage, bioassay efficacy and desirability compared with ordinary polyester nets., Results: Of 103 randomly selected nets distributed in 1994 to 1995, 100 could be traced. Most nets were in a condition likely to offer protection against mosquito biting. Villagers appreciated mainly the durability of Olyset trade mark nets and insecticide persistence. People disliked the small size of these nets and the light blue colour and preferred a smaller mesh size, features that can easily be modified. At equal price, 51% said they would prefer to buy an Olyset net and 49% opted for an ordinary polyester net. The average permethrin content was 33%-41% of the initial insecticide dose of 20,000 mg/Kg. Bioassay results indicated high knock-down rates at 60 minutes, but the mosquito mortality after 24 hours was rather low (mean: 34%). No significant correlation was found between bioassay results and insecticide concentration in and on the net., Conclusions: Olyset nets are popular, durable and with a much longer insecticide persistence than ordinary polyester nets. Hence, Olyset nets are one of the best choices for ITN programmes in rural malaria-endemic areas.

Insecticide-treated nets (ITNs) impregnated with pyrethroid insecticides have become one of the most promising interventions to prevent malaria in highly endemic areas. Despite the large body of experience documenting their health impact and the best way to distribute them, some key practical issues remain unresolved. For example, the duration of effective life of a net under field conditions is unknown. The most important factor affecting net effectiveness is the issue of regular re-treatment with insecticide. Washing is also an important determinant of insecticide longevity in the field. Trials were undertaken to provide some essential field information on ITNs within the site of an extended ITN programme in the Morogoro region of Tanzania. It was found that 45% of all nets were in bad condition (defined as more than seven large holes). It is concluded that an effective 'life' for polyester nets is 2-3 years. Further, two-thirds of the 20% of nets that were reported as having been re-treated within the last 12 months had less than 5 mg/m(2) of insecticide. According to the World Health Organization this is insufficient to be effective. People reported that they washed their nets four to seven times per year, usually with soap. Observations showed that such washing does not harm the nets and that the wash-water was unlikely to have an impact on the environment. Finally, bioassays were carried out with Anopheles gambiae on polyester netting with 0.5, 2, 5, 10 and 30 mg/m(2) of deltamethrin, alphacypermethrin and lambdacyhalothrin to assess the effectiveness of pyrethroids. The results confirmed that even with low insecticide concentrations, nets can still provide partial protection.

Background: Insecticide-treated nets have proven efficacy as a malaria-control tool in Africa. However, the transition from efficacy to effectiveness cannot be taken for granted. We assessed coverage and the effect on child survival of a large-scale social marketing programme for insecticide-treated nets in two rural districts of southern Tanzania with high perennial malaria transmission., Methods: Socially marketed insecticide-treated nets were introduced step-wise over a 2-year period from May, 1997, in a population of 480000 people. Cross-sectional coverage surveys were done at baseline and after 1, 2, and 3 years. A demographic surveillance system (DSS) was set up in an area of 60000 people to record population, births, and deaths. Within the DSS area, the effect of insecticide-treated nets on child survival was assessed by a case-control approach. Cases were deaths in children aged between 1 month and 4 years. Four controls for each case were chosen from the DSS database. Use of insecticide-treated nets and potential confounding factors were assessed by questionnaire. Individual effectiveness estimates from the case-control study were combined with coverage to estimate community effectiveness., Findings: Insecticide-treated net coverage of infants in the DSS area rose from less than 10% at baseline to more than 50% 3 years later. Insecticide-treated nets were associated with a 27% increase in survival in children aged 1 month to 4 years (95% CI 3-45). Coverage in such children was higher in areas with longer access to the programme. The modest average coverage achieved by 1999 in the two districts (18% in children younger than 5 years) suggests that insecticide-treated nets prevented 1 in 20 child deaths at that time., Interpretation: Social marketing of insecticide-treated nets has great potential for effective malaria control in rural African settings.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.

Background: Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania., Methods: The study was a two-arm, double blind, individually randomized placebo controlled trial involving 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 given at 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through a health facility-based passive case detection system., Results: Among 1207 randomized children, overall compliance for third dose was 91%. SPf66 was safe, immunogenic and did not interfere with the humoral immune responses to EPI vaccines. There were 294 children among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding a vaccine efficacy estimate of 2% (95% CI: -16, 16; P = 0.84)., Conclusion: This has been the first trial of a malaria vaccine among very young infants. It provides information on the safety of peptide vaccines administered at this early age as well as their capacity to induce immune responses without negatively interacting with EPI vaccines. Given the modest protection previously documented in older age groups and the lack of efficacy in younger infants, this vaccine in its current alum-based formulation does not appear to have a role in malaria control in sub-Saharan Africa. The lack of efficacy found in this trial also raises concerns about potential difficulties of inducing protective immune responses against malaria through immunization in infants.

The most likely mechanism to deliver a malaria vaccine in African countries is through the Expanded Program of Immunization (EPI). So far only SPf66, a multistage synthetic peptide, has shown any evidence of protection in Phase III field trials. In Tanzania, SPf66 reduced the risk of clinical malaria by 31% in children aged 1-5 years. In order to progress in the critical path of vaccine development and testing towards the implementation of a new vaccine in malaria control programs, we carried out a randomized double-blind placebo controlled efficacy trial of SPf66 when given alongside the EPI scheme. Monitoring of safety and reactogenicity during this trial included detailed clinical and laboratory assessments on 98 infants and assessment of adverse effects within 1 h of vaccination for all 1207 children vaccinated. Surveillance systems monitored attendances as outpatients, admissions to hospital and fatal events in the community. No serious adverse effects were detected more frequently amongst SPf66 recipients compared to placebo. This first assessment in very young infants of a synthetic vaccine provides evidence of a good safety profile.

Studies in vitro among children on the response of Plasmodium falciparum to chloroquine were conducted as part of the national long-term monitoring of drug resistance in a holo- to hyperendemic malarious area of Tanzania between 1983 and 1989. Overall, no significant increase in chloroquine resistance was observed. However, in children under 5 years old resistance increased during this period, whereas in schoolchildren resistance decreased from 1986 to 1989. A hypothesis based on antigenic differences between resistant and sensitive strains is proposed to explain this age-specific pattern. If immunity develops principally against the most frequent parasite strains, then as it develops the numbers of the most frequent strains will be reduced, whilst, the rare strains may become predominant and thus be detected in the blood of immune patients. Thus, in an endemic area, the observed resistance pattern in non-immune infants will differ from that in immune schoolchildren, as was observed in the present study. These findings may have important implications for the control of malaria and the development of vaccines.

Abstract Background Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank’s proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.