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Background: The response to antimalarial treatment is assessed using serial microscopy. New techniques for accurate measurement of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen have allowed for monitoring of the antigen concentration over time, offering a potential alternative for assessing treatment response.Methods: Posttreatment HRP2 concentrations were measured in samples obtained longitudinally from 537 individuals with P. falciparum malaria who were participating in efficacy trials in Angola, Tanzania, and Senegal. The HRP2 half-life was estimated using a first-order kinetics clearance model. The association between the HRP2 concentration 3 days after treatment and recrudescence of infection was assessed.Results: Despite substantial variation in HRP2 concentrations among participants at baseline, concentrations consistently showed a first-order exponential decline. The median half-life of HRP2 was estimated to be 4.5 days (interquartile range [IQR], 3.3-6.6 days) in Angola, 4.7 days (IQR, 4.0-5.9 days) in Tanzania, and 3.0 days (IQR, 2.1-4.5 days) in Senegal. The day 3 HRP2 concentration was predictive of eventual recrudescence, with an area under the receiver operating characteristic curve of 0.86 (95% confidence interval, .73-.99).Conclusions: Consistent HRP2 clearance dynamics following successful antimalarial treatment imply a common underlying mechanism of biological clearance. Patients who ultimately did not respond to treatment did not exhibit this same pattern of clearance, even in the absence of other indications of inadequate response to treatment. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) recommends parasitologic confirmation of suspected malaria cases before treatment. Due to the limited availability of quality microscopy services, this recommendation has become scalable following increased use of antigen-detecting malaria rapid diagnostic tests (RDTs) in many malaria-endemic countries. This study was carried out to monitor quality of RDT performance in selected health facilities using two quality assurance (QA) methods: reference microscopy and detection of parasite DNA by real-time quantitative polymerase chain reaction (qPCR) on dried blood spots (DBS). Methods: Blood samples for QA were collected from patients undergoing RDT for diagnostic confirmation of malaria during two to three consecutive days per month in 12 health facilities in rural Tanzania. Stained blood smears (BS) were first examined at the district hospitals (BS1) and then at a reference laboratory (BS2). Discordant BS1 and BS2 results prompted a third examination. Molecular analysis was carried out at the Ifakara Health Institute laboratory in Bagamoyo. Results: Malaria RDTs had a higher positivity rate (6.5%) than qPCR (4.2%) or microscopy (2.9% for BS1 and 2.5% for BS2). Poor correlation was observed between RDT and BS results: BS1 (K = 0.5), BS2 (K = 0.43) and qPCR (K = 0.45), challenging the utility of these tests for RDT QA. In addition, many challenges related to qPCR processing were recorded and long delays in obtaining QA test results for both microscopy and qPCR. Conclusions: Overall there was limited agreement among the three diagnostic approaches and neither microscopy nor qPCR appear to be good QA options for RDTs under field conditions. [ABSTRACT FROM AUTHOR]

Background: The Affordable Medicines Facility - malaria (AMFm) is primarily an artemisinin combination therapy (ACT) subsidy, aimed at increasing availability, affordability, market share and use of quality-assured ACTs (QAACTs). Mainland Tanzania was one of eight national scale programmes where AMFm was introduced in 2010. Here we present findings from outlet and household surveys before and after AMFm implementation to evaluate its impact from both the supply and demand side. Methods: Outlet surveys were conducted in 49 randomly selected wards throughout mainland Tanzania in 2010 and 2011, and data on outlet characteristics and stocking patterns were collected from outlets stocking antimalarials. Household surveys were conducted in 240 randomly selected enumeration areas in three regions in 2010 and 2012. Questions about treatment seeking for fever and drugs obtained were asked of individuals reporting fever in the previous two weeks. Results: The availability of QAACTs increased from 25.5% to 69.5% among all outlet types, with the greatest increase among pharmacies and drug stores, together termed specialised drug sellers (SDSs), where the median QAACT price fell from $5.63 to $0.94. The market share of QAACTs increased from 26.2% to 42.2%, again with the greatest increase in SDSs. Household survey results showed a shift in treatment seeking away from the public sector towards SDSs. Overall, there was no change in the proportion of people with fever obtaining an antimalarial or ACT from baseline to endline. However, when broken down by treatment source, ACT use increased significantly among clients visiting SDSs. Discussion: Unchanged ACT use overall, despite increases in QAACT availability, affordability and market share in the private sector, reflected a shift in treatment seeking towards private providers. The reasons for this shift are unclear, but likely reflect both persistent stockouts in public facilities, and the increased availability of subsidised ACTs in the private sector. [ABSTRACT FROM AUTHOR]

Background: Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. Method and Findings: A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6–18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was <5 years old (aOR: 6.6; 95% CI: 3.9–11.0) or the shop attendant had >5 years, experience (aOR: 2.8; 95% CI: 1.2–6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5–7.4). Conclusion: Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria. Methods Exit interviews were conducted with patients attending health facilities for initial illness consultation. Information about health workers' training and supervision visits was collected. Health facilities were inventoried for capacity and availability of medical products related to care of malaria patients. The outcome was correct dosing of AL based on age and weight. Logistic regression was used to assess health facility factors and patient characteristics associated with correct dosing of AL by age and weight. Results A total of 1,531 patients were interviewed, but 60 pregnant women were excluded from the analysis. Only 503 (34.2%) patients who received AL were assessed for correct dosing. Most patients who received AL (85.3%) were seen in public health facilities, 75.7% in a dispensary and 91.1% in a facility that had AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were correct by age or weight; but 85.7% of patients received correct dosing by weight alone and 78.5% received correct dosing by age alone. In multivariate analysis, patients in the middle dosing bands in terms of age or weight, had statistically significant lower odds of correct AL dosing (p < 0.05) compared to those in the lowest age or weight group. Other factors such as health worker supervision and training on ACT did not improve the odds of correct AL dosing. Conclusion Although malaria treatment guidelines indicate AL dosing can be prescribed based on age or weight of the patient, findings from this study show that patients within the middle age and weight dosing bands were least likely to receive a correct dose by either measure. Clinicians should be made aware of AL dosing errors for patients aged three to 12 years and advised to use weight-based prescriptions whenever possible. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. Methods: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 h and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a non-febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT.Results: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p = 0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p < 0.01) in high transmission. The odds of over treatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67). Conclusion: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc.) may be needed to improve ACT targeting during low transmission seasons. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) represent the front-line tools for malaria vector control globally, but are optimally effective where the majority of baseline transmission occurs indoors. In the surveyed area of rural southern Tanzania, bed net use steadily increased over the last decade, reducing malaria transmission intensity by 94%. Methods: Starting before bed nets were introduced (1997), and then after two milestones of net use had been reached-75% community-wide use of untreated nets (2004) and then 47% use of ITNs (2009)-hourly biting rates of malaria vectors from the Anopheles gambiae complex and Anopheles funestus group were surveyed. Results: In 1997, An. gambiae s.l. and An. funestus mosquitoes exhibited a tendency to bite humans inside houses late at night. For An. gambiae s.l., by 2009, nocturnal activity was less (p = 0.0018). At this time, the sibling species composition of the complex had shifted from predominantly An. gambiae s.s. to predominantly An. arabiensis. For An. funestus, by 2009, nocturnal activity was less (p = 0.0054) as well as the proportion biting indoors (p < 0.0001). At this time, An. funestus s.s. remained the predominant species within this group. As a consequence of these altered feeding patterns, the proportion (mean ± standard error) of human contact with mosquitoes (bites per person per night) occurring indoors dropped from 0.99 ± 0.002 in 1997 to 0.82 ± 0.008 in 2009 for the An. gambiae complex (p = 0.0143) and from 1.00 ± <0.001 to only 0.50 ± 0.048 for the An. funestus complex (p = 0.0004) over the same time period. Conclusions: High usage of ITNs can dramatically alter African vector populations so that intense, predominantly indoor transmission is replaced by greatly lowered residual transmission, a greater proportion of which occurs outdoors. Regardless of the underlying mechanism, the residual, self-sustaining transmission will respond poorly to further insecticidal measures within houses. Additional vector control tools which target outdoor biting mosquitoes at the adult or immature stages are required to complement ITNs and IRS. [ABSTRACT FROM AUTHOR]

Introduction: Retail pharmaceutical products are commonly used to treat fever and malaria in sub-Saharan African countries. Small scale studies have suggested that poor quality antimalarials are widespread throughout the region, but nationwide data are not available that could lead to generalizable conclusions about the extent to which poor quality drugs are available in African communities. This study aimed to assess the quality of antimalarials available from retail outlets across mainland Tanzania. Methods and Findings: We systematically purchased samples of oral antimalarial tablets from retail outlets across 21 districts in mainland Tanzania in 2005. A total of 1080 antimalarial formulations were collected including 679 antifol antimalarial samples (394 sulfadoxine/pyrimethamine and 285 sulfamethoxypyrazine/pyrimethamine), 260 amodiaquine samples, 63 quinine samples, and 51 artemisinin derivative samples. A systematic subsample of 304 products was assessed for quality by laboratory based analysis to determine the amount of the active ingredient and dissolution profile by following the published United States Pharmacopoeia (USP) monogram for the particular tablet being tested. Products for which a published analytical monogram did not exist were assessed on amount of active ingredient alone. Overall 38 or 12.2% of the samples were found to be of poor quality. Of the antifolate antimalarial drugs tested 13.4% were found to be of poor quality by dissolution and content analysis using high-performance liquid chromatography (HPLC). Nearly one quarter (23.8%) of quinine tablets did not comply within the tolerance limits of the dissolution and quantification analysis. Quality of amodiaquine drugs was relatively better but still unacceptable as 7.5% did not comply within the tolerance limits of the dissolution analysis. Formulations of the artemisinin derivatives all contained the stated amount of active ingredient when analysed using HPLC alone. Conclusions: Substandard antimalarial formulations were widely available in Tanzania at the time of this study. No products were detected that did not contain any amount of the stated active ingredient. Quinine and sulfadoxine/pyrimethamine products were the most widely available and also the most likely to be of poor quality. Substandard products were identified in all parts of the country and were labeled as made by both domestic and international manufacturers. With the expansion of the retail pharmaceutical sector as a delivery channel for antimalarial formulations the need for regular nationwide monitoring of their quality will become increasingly important. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 to1 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. [ABSTRACT FROM AUTHOR]

Background: The development of antimalarial drug resistance has led to increasing calls for the introduction of artemisinin-based combination therapy (ACT). However, little evidence is available on the full costs associated with changing national malaria treatment policy. This paper presents findings on the actual drug and non-drug costs associated with deploying ACT in one district in Tanzania, and uses these data to estimate the nationwide costs of implementation in a setting where identification of malaria cases is primarily dependant on clinical diagnosis. Methods: Detailed data were collected over a three year period on the financial costs of providing ACT in Rufiji District as part of a large scale effectiveness evaluation, including costs of drugs, distribution, training, treatment guidelines and other information, education and communication (IEC) materials and publicity. The district-level costs were scaled up to estimate the costs of nationwide implementation, using four scenarios to extrapolate variable costs. Results: The total district costs of implementing ACT over the three year period were slightly over one million USD, with drug purchases accounting for 72.8% of this total. The composite (best) estimate of nationwide costs for the first three years of ACT implementation was 48.3 million USD (1.29 USD per capita), which varied between 21 and 67.1 million USD in the sensitivity analysis (2003 USD). In all estimates drug costs constituted the majority of total costs. However, non-drug costs such as IEC materials, drug distribution, communication, and health worker training were also substantial, accounting for 31.4% of overall ACT implementation costs in the best estimate scenario. Annual implementation costs are equivalent to 9.5% of Tanzania's recurrent health sector budget, and 28.7% of annual expenditure on medical supplies, implying a 6-fold increase in the national budget for malaria treatment. Conclusion: The costs of implementing ACT are substantial. Although drug purchases constituted a majority of total costs, non-drug costs were also considerable. It is clear that substantial external resources will be required to facilitate and sustain effective ACT delivery across Tanzania and other malaria-endemic countries. [ABSTRACT FROM AUTHOR]

Regulatory infringements are extremely common in low-income countries, especially with respect to retail pharmaceutical sales. There have been few practical suggestions on public policy responses other than stricter regulatory enforcement, which governments are often unable, or unwilling, to do. This paper explores the challenges of regulating retail drug sellers, and potential solutions, through a case study of malaria treatment in rural Tanzania where small drug shops are a common source of medicine. [ABSTRACT FROM PUBLISHER]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To determine the prevalence of malaria parasitemia and other common illnesses among drug store clients in one rural community, with a view to the potential role of specialist drug stores in expanding coverage of effective malaria treatment to households in highly endemic areas. Method Follow-back study of 2466 client visits selected from all 10 drug stores operating in the town of Ikwiriri between May 30 and August 31 2004. Of these, 521 (21.2%) were made by or on behalf of persons ill with fever or malaria. Two hundred and ninety three were eligible as residents of the surrounding nine villages and all agreed to participate in the study. Each patient was evaluated by a clinical officer and provided a blood sample for malaria on the day of the shop visit, either at the shop or at home. Results Only 50 (17.1%) visits by or on behalf of febrile patients resulted in the purchase of an antimalarial drug, while an antipyretic medication was obtained at 226 visits (77.1%). Clinicians diagnosed malaria in 63.8% of patients. Malaria parasites were identified in blood film samples from 24.2% (95% CI: 19.6, 29.5). This is double the parasite prevalence rate of 10.7% (95% CI: 8.6, 13.1) obtained from a household survey of 1004 healthy individuals selected from these villages at the same time. It is not significantly lower than the prevalence observed among 880 clients presenting with fever at health facilities in the district: 29.7% (95% CI: 23.0, 37.3). The prevalence of malaria parasitemia among children younger than 5 years whose families sought fever treatment from drug stores (42.1%; 95% CI: 31.4, 53.5) was equal to that of children presenting with fever at health facilities (42.5%; 95% CI: 25.0, 62.2). Conclusions Currently, drug store clients do not obtain malaria-specific treatment in the majority of cases where it might be warranted. Parasitological findings indicate that drug store clients, especially children, are as likely to be infected with malaria as patients seeking care for similar illnesses at health facilities. Drug stores may be attractive partners for policy makers eager to engage the private retail sector in expanding coverage of malaria treatment. [ABSTRACT FROM AUTHOR]

Background: Recently global health advocates have called for the introduction of artemisinincontaining antimalarial combination therapies to help curb the impact of drug-resistant malaria in Africa. Retail trade in artemisinin monotherapies could undermine efforts to restrict this class of medicines to more theoretically sound combination treatments. Methods: This paper describes a systematic search for artemisinin-containing products at a random sample of licensed pharmacies in Dar-es-Salaam, Tanzania in July 2005. Results: Nineteen different artemisinin-containing oral pharmaceutical products, including one coformulated product, one co-packaged product, and 17 monotherapies were identified. All but one of the products were legally registered and samples of each product were obtained without a prescription. Packaging and labeling of the products seldom included local language or illustrated instructions for low-literate clients. Packaging and inserts compared reasonably well with standards recommended by the national regulatory authority with some important exceptions. Dosing instructions were inconsistent, and most recommended inadequate doses based on international standards. None of the monotherapy products mentioned potential benefits of combining the treatment with another antimalarial drug. Conclusion: The findings confirm the widespread availability of artemisinin monotherapies that led the World Health Organization to call for the voluntary withdrawal of these drugs in malariaendemic countries. As the global public health community gathers resources to deploy artemisinincontaining combination therapies in Africa, planners should be mindful that these drugs will coexist with artemisinin monotherapies in an already well-established market place. In particular, regulatory authorities should be incorporated urgently into the process of planning for rational deployment of artemisinin-containing antimalarial combination therapies. [ABSTRACT FROM AUTHOR]

Background: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. Methods: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. Results: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment.Conclusion: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population. [ABSTRACT FROM AUTHOR]

To characterize availability of fever and malaria medicines within the retail sector in rural Tanzania, assess the likely public health implications, and identify opportunities for policy interventions to increase the coverage of effective treatment. A census of retailers selling drugs was undertaken in the areas under demographic surveillance in four Tanzanian districts, using a structured questionnaire. Drugs were stocked by two types of retailer: a large number of general retailers ( n = 675) and a relatively small number of drug shops ( n = 43). Almost all outlets stocked antipyretics/painkillers. One-third of general retailers stocking drugs had antimalarials, usually chloroquine alone. Almost all drug shops stocked antimalarials (98%): nearly all had chloroquine, 42% stocked quinine, 37% sulphadoxine–pyrimethamine and 30% amodiaquine. A large number of antimalarial brands were available. Population ratios indicate the relative accessibility of retail drug providers compared with health facilities. Drug shop staff generally travelled long distances to buy from drugs wholesalers or pharmacies. General retailers bought mainly from local general wholesalers, with a few general wholesalers accounting for a high proportion of all sources cited. Drugs were widely available from a large number of retail outlets. Potential negative implications include provision of ineffective drugs, confusion over brand names, uncontrolled use of antimalarials, and the availability of components of potential combination therapy regimens as monotherapies. On the other hand, this active and highly accessible retail market provides opportunities for improving the coverage of effective antimalarial treatment. Interventions targeted at all drug retailers are likely to be costly to deliver and difficult to sustain, but two promising points for targeted intervention are drug shops and selected general wholesalers. Retail quality may also be improved through consumer education, and modification of the chemical quality, packaging and price of products entering the retail distribution chain. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesized that in high-transmission settings, malaria control in early childhood (<5 years of age) might delay the acquisition of functional immunity and shift child deaths from younger to older ages.Methods: We used data from a 22-year prospective cohort study in rural southern Tanzania to estimate the association between early-life use of treated nets and survival to adulthood. All the children born between January 1, 1998, and August 30, 2000, in the study area were invited to enroll in a longitudinal study from 1998 through 2003. Adult survival outcomes were verified in 2019 through community outreach and mobile telephones. We used Cox proportional-hazards models to estimate the association between the use of treated nets in early childhood and survival to adulthood, adjusting for potential confounders.Results: A total of 6706 children were enrolled. In 2019, we verified information on the vital status of 5983 participants (89%). According to reports of early-life community outreach visits, approximately one quarter of children never slept under a treated net, one half slept under a treated net some of the time, and the remaining quarter always slept under a treated net. Participants who were reported to have used treated nets at half the early-life visits or more had a hazard ratio for death of 0.57 (95% confidence interval [CI], 0.45 to 0.72) as compared with those who were reported to have used treated nets at less than half the visits. The corresponding hazard ratio between 5 years of age and adulthood was 0.93 (95% CI, 0.58 to 1.49).Conclusions: In this long-term study of early-life malaria control in a high-transmission setting, the survival benefit from early-life use of treated nets persisted to adulthood. (Funded by the Eckenstein-Geigy Professorship and others.). [ABSTRACT FROM AUTHOR]

Objective To determine why health workers fail to follow integrated management of childhood illness (IMCI) guidelines for severely ill children at first-level outpatient health facilities in rural areas of the United Republic of Tanzania. Methods Retrospective and prospective case reviews of severely ill children aged < 5 years were conducted at health facilities in four districts. We ascertained treatment and examined the characteristics associated with referral, conducted follow-up interviews with parents of severely ill children, and gave health workers questionnaires and interviews. Findings In total, 502 cases were reviewed at 62 facilities. Treatment with antimalarials and antibiotics was consistent with the diagnosis given by health workers. However, of 240 children classified as having "very severe febrile disease", none received all IMCI-recommended therapies, and only 25% of severely ill children were referred. Lethargy and anaemia diagnoses were independently associated with referral. Most (91%) health workers indicated that certain severe conditions can be managed without referral. Conclusion The health workers surveyed rarely adhered to IMCI treatment and referral guidelines for children with severe illness. They administered therapy based on narrow diagnoses rather than IMCI classifications, disagreed with referral guidelines and often considered referral unnecessary. To improve implementation of IMCI, attention should focus on the reasons for health worker non-adherence. [ABSTRACT FROM AUTHOR]

Background: Self-report is the most common and feasible method for assessing patient adherence to medication, but can be prone to recall bias and social desirability bias. Most studies assessing adherence to artemisinin-based combination therapies (ACTs) have relied on self-report. In this study, we use a novel customised electronic monitoring device--termed smart blister packs--to examine the validity of self-reported adherence to artemether-lumefantrine (AL) in southern Tanzania., Methods: Smart blister packs were designed to look identical to locally available AL blister packs and to record the date and time each tablet was removed from packaging. Patients obtaining AL at randomly selected health facilities and drug stores were followed up at home three days later and interviewed about each dose of AL taken. Blister packs were requested for pill count and extraction of smart blister pack data., Results: Data on adherence from both self-report verified by pill count and smart blister packs were available for 696 of 1,204 patients. There was no difference between methods in the proportion of patients assessed to have completed treatment (64% and 67%, respectively). However, the percentage taking the correct number of pills for each dose at the correct times (timely completion) was higher by self-report than smart blister packs (37% vs. 24%; p<0.0001). By smart blister packs, 64% of patients completing treatment did not take the correct number of pills per dose or did not take each dose at the correct time interval., Conclusion: Smart blister packs resulted in lower estimates of timely completion of AL and may be less prone to recall and social desirability bias. They may be useful when data on patterns of adherence are desirable to evaluate treatment outcomes. Improved methods of collecting self-reported data are needed to minimise bias and maximise comparability between studies.

Background: Artemisinin combination therapy (ACT) is first-line treatment for malaria in most endemic countries and is increasingly available in the private sector. Most studies on ACT adherence have been conducted in the public sector, with minimal data from private retailers., Methods: Parallel studies were conducted in Tanzania, in which patients obtaining artemether-lumefantrine (AL) at 40 randomly selected public health facilities and 37 accredited drug dispensing outlets (ADDOs) were visited at home and questioned about doses taken. The effect of sector on adherence, controlling for potential confounders was assessed using logistic regression with a random effect for outlet., Results: Of 572 health facility patients and 450 ADDO patients, 74.5% (95% CI: 69.8, 78.8) and 69.8% (95% CI: 64.6, 74.5), respectively, completed treatment and 46.0% (95% CI: 40.9, 51.2) and 34.8% (95% CI: 30.1, 39.8) took each dose at the correct time ('timely completion'). ADDO patients were wealthier, more educated, older, sought care later in the day, and were less likely to test positive for malaria than health facility patients. Controlling for patient characteristics, the adjusted odds of completed treatment and of timely completion for ADDO patients were 0.65 (95% CI: 0.43, 1.00) and 0.69 (95% CI: 0.47, 1.01) times that of health facility patients. Higher socio-economic status was associated with both adherence measures. Higher education was associated with completed treatment (adjusted OR = 1.68, 95% CI: 1.20, 2.36); obtaining AL in the evening was associated with timely completion (adjusted OR = 0.35, 95% CI: 0.19, 0.64). Factors associated with adherence in each sector were examined separately. In both sectors, recalling correct instructions was positively associated with both adherence measures. In health facility patients, but not ADDO patients, taking the first dose of AL at the outlet was associated with timely completion (adjusted OR = 2.11, 95% CI: 1.46, 3.04)., Conclusion: When controlling for patient characteristics, there was some evidence that the adjusted odds of adherence for ADDO patients was lower than that for public health facility patients. Better understanding is needed of which patient care aspects are most important for adherence, including the role of effective provision of advice.

The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection., (© The American Society of Tropical Medicine and Hygiene.)

Background: The last decade has witnessed increased funding for malaria control. Malaria experts have used the opportunity to advocate for rollout of such interventions as free bed nets. A free bed net distribution strategy is seen as the quickest way to improve coverage of effective malaria control tools especially among poorest communities. Evidence to support this claim is however, sparse. This study explored the effectiveness of targeted free bed net distribution strategy in achieving equity in terms of ownership and use of bed nets and also reduction of malaria prevalence among children under-five years of age., Methods: National malaria indicator survey (MIS) data from Angola, Tanzania and Uganda was used in the analysis. Hierarchical multilevel logistic regression models were used to analyse the relationship between variables of interest. Outcome variables were defined as: childhood test-confirmed malaria infections, household ownership of any mosquito net and children's use of any mosquito nets. Marginal effects of having free bed net distribution on households with different wealth status were calculated., Results: Angolan children from wealthier households were 6.4 percentage points less likely to be parasitaemic than those in poorest households, whereas those from Tanzania and Uganda were less likely to test malaria positive by 7 and 11.6 percentage points respectively (p < 0.001). The study estimates and present results on the marginal effects based on the impact of free bed net distribution on children's malaria status given their socio-economic background. Poorest households were less likely to own a net by 21.4% in Tanzania, and 2.8% in Uganda, whereas both poorer and wealthier Angolan households almost achieved parity in bed net ownership (p < 0.001). Wealthier households had a higher margin of using nets than poorest people in both Tanzania and Uganda by 11.4% and 3.9% respectively. However, the poorest household in Angola had a 6.1% net use advantage over children in wealthier households (p < 0.001)., Conclusion: This is the first study to use nationally representative data to explore inequalities in bed net ownership and related consequences on childhood malaria infection rates across different countries. While targeted distribution of free bed nets improved overall bed net ownership, it did not overcome ownership inequalities as measured by household socioeconomic status. Use of bed nets was disproportionately lower among poorest children, except for Angola where bed net use was higher among poorest households when compared to children in wealthier households. The study highlights the need for malaria control world governing bodies and policy makers to continue working on finding appropriate strategies to improve access to effective malaria control tools especially by the poorest who often times bears the brunt of malaria burden than their wealthier counterparts.

Background: Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems., Methods: Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having 'possible' or 'probable' ADR by a physician., Results: A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as 'probable' and 33 as 'possible' ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on 'probable' ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money., Conclusion: Both passive and active surveillance methods proved feasible methods for anti-malarial ADR surveillance, with active surveillance being an important complement to facility-based surveillance, given the widespread practice of self-medication. Household costs associated with ADR treatment were high and potentially catastrophic. Efforts should be made to both improve pharmacovigilance across Africa and to identify strategies to reduce the economic burden endured by households suffering from ADR.

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 <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30)., 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.

Accurate and rapid diagnosis of malaria infections is crucial for implementing species-appropriate treatment and saving lives. Molecular diagnostic tools are the most accurate and sensitive method of detecting Plasmodium, differentiating between Plasmodium species, and detecting subclinical infections. Despite available whole-genome sequence data for Plasmodium falciparum and P. vivax, the majority of PCR-based methods still rely on the 18S rRNA gene targets. Historically, this gene has served as the best target for diagnostic assays. However, it is limited in its ability to detect mixed infections in multiplex assay platforms without the use of nested PCR. New diagnostic targets are needed. Ideal targets will be species specific, highly sensitive, and amenable to both single-step and multiplex PCRs. We have mined the genomes of P. falciparum and P. vivax to identify species-specific, repetitive sequences that serve as new PCR targets for the detection of malaria. We show that these targets (Pvr47 and Pfr364) exist in 14 to 41 copies and are more sensitive than 18S rRNA when utilized in a single-step PCR. Parasites are routinely detected at levels of 1 to 10 parasites/μl. The reaction can be multiplexed to detect both species in a single reaction. We have examined 7 P. falciparum strains and 91 P. falciparum clinical isolates from Tanzania and 10 P. vivax strains and 96 P. vivax clinical isolates from Venezuela, and we have verified a sensitivity and specificity of ∼100% for both targets compared with a nested 18S rRNA approach. We show that bioinformatics approaches can be successfully applied to identify novel diagnostic targets and improve molecular methods for pathogen detection. These novel targets provide a powerful alternative molecular diagnostic method for the detection of P. falciparum and P. vivax in conventional or multiplex PCR platforms.

Histidine-rich protein II (HRP2)-based malaria rapid diagnostic tests (RDTs) have shown high sensitivity and specificity for detecting Plasmodium falciparum malaria in a variety of study settings. However, RDTs are susceptible to heat and humidity and variation in individual performance, which may affect their use in field settings. We evaluated sensitivity and specificity of RDTs during routine use for malaria case management in peripheral health facilities. From December 2007 to October 2008, HRP2-based ParaHIT-f RDTs were introduced in 12 facilities without available microscopy in Rufiji District, Tanzania. Health workers received a single day of instruction on how to perform an RDT and thick blood smear. Job aids, Integrated Management of Childhood Illness guidelines, and national malaria treatment algorithms were reviewed. For quality assurance (QA), thick blood smears for reference microscopy were collected for 2 to 3 days per week from patients receiving RDTs; microscopy was not routinely performed at the health facilities. Slides were stained and read centrally within 72 hours of collection by a reference microscopist. When RDT and blood smear results were discordant, blood smears were read by additional reference microscopists blinded to earlier results. Facilities were supervised monthly by the district laboratory supervisor or a member of the study team. Ten thousand six hundred fifty (10,650) patients were tested with RDTs, and 51.5% (5,488/10,650) had a positive test result. Blood smear results were available for 3,914 patients, of whom 40.1% (1,577/3,914) were positive for P. falciparum malaria. Overall RDT sensitivity was 90.7% (range by facility 85.7-96.5%) and specificity was 73.5% (range 50.0-84.3%). Sensitivity increased with increasing parasite density. Successful implementation of RDTs was achieved in peripheral health facilities with adequate training and supervision. Quality assurance is essential to the adequate performance of any laboratory test. Centralized staining and reading of blood smears provided useful monitoring of RDT performance. However, this level of QA may not be sustainable nationwide.

The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care-seekers obtaining appropriate treatment.Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Background: Malaria rapid diagnostic tests (RDTs) may assist in diagnosis, improve prescribing practices and reduce potential drug resistance development. Without understanding operational issues or acceptance and usage by providers and patients, the costs of these tests may not be justified., Objectives: To evaluate the impact of RDTs on prescribing behaviours, assess prescribers' and patients' perceptions, and identify operational issues during implementation., Methods: Baseline data were collected at six Tanzanian public dispensaries. RDTs were implemented for eight weeks and data collected on frequency of RDT use, results, malaria diagnoses and the prescription of antimalarials. Patients referred for RDTs completed a standardised exit interview. Qualitative methods assessed attitudes toward and satisfaction with RDTs, perceptions about the test and operational issues related to implementation., Results: Of 595 patients at baseline, 200 (33%) were diagnosed clinically with malaria but had a negative RDT. Among the 2519 RDTs performed during implementation, 289 (11.5%) had a negative result and antimalarials prescribed. The proportion of "over-prescriptions" at baseline was 54.8% (198/365). At weeks four and eight this decreased to 16.1% (27/168) and 16.4% (42/256) respectively.A total of 355 patient or parent/caregiver and 21 prescriber individual interviews and 12 focus group discussions (FGDs) were conducted. Patients, caregivers and providers trusted RDT results, agreed that use of RDTs was feasible at dispensary level, and perceived that RDTs improved clinical diagnosis. Negative concerns included community suspicion and fear that RDTs were HIV tests, the need for additional supervision in interpreting the results, and increased work loads without added compensation., Conclusion: Overprescriptions decreased over the study period. There was a high degree of patient/caregiver and provider acceptance of and satisfaction with RDTs. Implementation should include community education, sufficient levels of training and supervision and consideration of the need for additional staff.

Rapid diagnostic tests (RDTs) represent an alternative to microscopy for malaria diagnosis and have shown high sensitivity and specificity in a variety of study settings. Current World Health Organization (WHO) guidelines for quality control of RDTs provide detailed instructions on pre-field testing, but offer little guidance for quality assurance once RDTs are deployed in health facilities. From September 2006 to April 2007, we introduced a histidine-rich protein II (HRP2)-based RDT (Paracheck) for suspected malaria cases five years of age and older in nine health facilities in Rufiji District, Tanzania, to assess sensitivity and specificity of RDTs in routine use at rural health facilities. Thick blood smears were collected for all patients tested with RDTs and stained and read by laboratory personnel in each facility. Thick smears were subsequently reviewed by a reference microscopist to determine RDT sensitivity and specificity. In all nine health facilities, there were significant problems with the quality of staining and microscopy. Sensitivity and specificity of RDTs were difficult to assess given the poor quality of routine blood smear staining. Mean operational sensitivity of RDTs based on reference microscopy was 64.8%, but varied greatly by health facility, range 18.8-85.9%. Sensitivity of RDTs increased with increasing parasite density. Specificity remained high at 87.8% despite relatively poor slide quality. Institution of quality control of RDTs based on poor quality blood smear staining may impede reliable measurement of sensitivity and specificity and undermine confidence in the new diagnostic. There is an urgent need for the development of alternative quality control procedures for rapid diagnostic tests that can be performed at the facility level.

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.

Malaria's relationship with socioeconomic status at the macroeconomic level has been established. This is the first study to explore this relationship at the microeconomic (household) level and estimate the direction of association. Malaria prevalence was measured by parasitemia, and household socioeconomic status was measured using an asset based index. Results from an instrumental variable probit model suggest that socioeconomic status is negatively associated with malaria parasitemia. Other variables that are significantly associated with parasitemia include age of the individual, use of a mosquito net on the night before interview, the number of people living in the household, whether the household was residing at their farm home at the time of interview, household wall construction, and the region of residence. Matching estimators indicate that malaria parasitemia is associated with reduced household socioeconomic status.

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

Use of insecticide-treated bednets (ITNs) to prevent malaria remains low, and effective distribution strategies are needed. An integrated child health campaign with free distribution of 162,254 untreated bednets bundled with insecticide, measles vaccination, vitamin A, and mebendazole for children < 5 years old ("under-5s") was conducted in Lindi Region, Tanzania. We conducted a representative household survey 3 months after the campaign. Altogether, 574 households with 354 under-5s were visited. In households with an under-5, possession of bednets and ITNs increased from 60.9% to 90.7% (P < 0.001) and from 16.5% to 37.3% (P < 0.001), respectively. Increases occurred in all wealth quintiles and equity improved. Reported bednet and ITN use the previous night among under-5s was 46.3% and 21.5%, respectively. Integrated campaigns rapidly and equitably increase bednet possession and use meriting continued large-scale implementation. However, our study found that bednets were rarely treated; thus, future campaigns should provide factory-treated long-lasting ITNs. Low ITN use underscores the need for further efforts to increase use after campaigns.