Long-term impact of rotavirus vaccination on all-cause and rotavirus-specific gastroenteritis and strain distribution in Central Kenya: An 11-year interrupted time-series analysis.

BACKGROUND: Kenya introduced a monovalent rotavirus vaccine administered orally at 6 and 10 weeks of age into her National Immunization Program in July 2014. The study evaluated the long-term impact of the vaccine on hospitalization for all-cause and rotavirus-specific acute gastroenteritis (AGE) and strain epidemiology in Kenya. METHODS: Data on all-cause and rotavirus-specific AGE and strain distribution were derived from an eleven-year hospital-based surveillance of AGE among children aged <5 years at Kiambu County Teaching and Referral Hospital (KCTRH) in Central Kenya between 2009 and 2020. Fecal samples were screened for group A rotavirus using ELISA and genotyped using multiplex semi-nested RT-PCR. Trends in all-cause and rotavirus-related AGE and strain distribution were compared between the pre-vaccine (July 2009-June 2014), early post-vaccine (July 2014-June 2016) and late post-vaccine (February 2019-October 2020) periods. RESULTS: Rotavirus-specific AGE was detected at 27.5% (429/1546, 95% CI: 25.5-30.1%) in the pre-vaccine period; 13.8% (91/658, 95% CI: 11.3-16.6%) in the early post-vaccine period (July 2014-June 2016); and 12.0% (229/1916, 95% CI: 10.6-13.5%) in the late post-vaccine period (February 2019-October 2020). This amounted to a decline of 49.8% (95% CI: 34.6%-63.7%) in rotavirus-specific AGE in the early post-vaccine period and 53.4% (95% CI: 41.5-70.3%) in the late post-vaccine period when compared to the pre-vaccine period. All-cause AGE hospitalizations declined by 40.2% (95% CI: 30.8%-50.2%) and 75.3% (95% CI: 65.9-83.1%) in the early post-vaccine and late post-vaccine periods, respectively, when compared to the pre-vaccine period. G3P [8] was the predominant strain in the late post-vaccine period, replacing G1P[8] which had predominated in the pre-vaccine and early post-vaccine periods. Additionally, we detected considerable proportions of uncommon strains G3P[6] (4.8%) and G12P[6] (3.5%) in the post-vaccine era. CONCLUSION: Rotavirus vaccination has resulted in a significant decline in all-cause and rotavirus-specific AGE, and thus, provides strong evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunization. However, the shift in strain dominance and age distribution of rotavirus AGE in the post-vaccine era underscores the need for continued surveillance to assess any possible vaccine-induced selective pressure that could diminish the vaccine effectiveness over time.

Mobilizing resources with an investment case to mitigate cross-border malaria transmission and achieve malaria elimination in South Africa.

South Africa's effort to eliminate malaria is significantly challenged by a large number of imported malaria cases, especially from neighbouring Mozambique. The country has a funding gap to achieve its malaria elimination goals (prior to 2019) and is ineligible to receive a national allocation from the Global Fund. The findings of an IC were utilised to successfully mobilise resources for malaria elimination in South Africa in 2018. A five-step resource mobilisation strategy was implemented to highlight financing challenges and leverage the economic evidence from an IC for malaria elimination in South Africa. South Africa's malaria programme implements control and elimination activities in three malaria-endemic provinces (KwaZulu Natal, Limpopo, and Mpumalanga). Driven by the IC findings, the South African government took an unprecedented step and increased total domestic malaria financing by approximately 36%, from the 2018/19 to the 2019/20 financial years through the creation of a new conditional grant for malaria. The IC findings predicted that malaria control in southern Mozambique is a prerequisite to eliminate malaria in South Africa. Based on this, the South African government also allocated funding towards a co-financing mechanism to support malaria control efforts in southern Mozambique. The IC findings assisted the South African National Department of Health to make a convincing case to key government decision-makers to invest in national malaria elimination and maximise economic returns in the long run. The South African government is the first in Southern Africa to mobilise a significant increase in domestic malaria financing to address the financial sustainability of both national and regional malaria elimination efforts. Continued surveillance activities will be required to prevent the re-establishment of malaria transmission even after malaria elimination is achieved in South Africa. Information sharing and close collaboration with provincial and national government officials were key to the successful outcome.

Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2×2 factorial design cluster randomised controlled trial.

OBJECTIVES: To estimate the cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in a low endemic setting. SETTING: The study was part of a 2×2 factorial design cluster randomised controlled trial within the catchment area of 11 primary health facilities in Zambezi, Namibia. PARTICIPANTS: Cost and outcome data were collected from the trial, which included 8948 community members that received interventions due to their residence within 500 m of malaria index cases. OUTCOME MEASURES: The primary outcome was incremental cost effectiveness ratio (ICER) per in incident case averted. ICER per prevalent case and per disability-adjusted life years (DALY) averted were secondary outcomes, as were per unit interventions costs and personnel time. Outcomes were compared as: (1) rfMDA versus RACD, (2) RAVC versus no RAVC and (3) rfMDA+RAVC versus RACD only. RESULTS: rfMDA cost 1.1× more than RACD, and RAVC cost 1.7× more than no RAVC. Relative to RACD only, the cost of rfMDA+RAVC was double ($3082 vs $1553 per event). The ICERs for rfMDA versus RACD, RAVC versus no RAVC and rfMDA+RAVC versus RACD only were $114, $1472 and $842, per incident case averted, respectively. Using prevalent infections and DALYs as outcomes, trends were similar. The median personnel time to implement rfMDA was 20% lower than for RACD (30 vs 38 min per person). The median personnel time for RAVC was 34 min per structure sprayed. CONCLUSION: Implemented alone or in combination, rfMDA and RAVC were cost effective in reducing malaria incidence and prevalence despite higher implementation costs in the intervention compared with control arms. Compared with RACD, rfMDA was time saving. Cost and time requirements for the combined intervention could be decreased by implementing rfMDA and RAVC simultaneously by a single team. TRIAL REGISTRATION NUMBER: NCT02610400; Post-results.

Genomic characterization of an African G4P[6] human rotavirus strain identified in a diarrheic child in Kenya: Evidence for porcine-to-human interspecies transmission and reassortment.

Human rotavirus strains having the unconventional G4P[6] genotype have been sporadically identified in diarrheic patients in different parts of the world. However, the whole genome of only one human G4P[6] strain from Africa (central Africa) has been sequenced and analyzed, and thus the exact origin and evolutionary pattern of African G4P[6] strains remain to be elucidated. In this study, we characterized the full genome of an African G4P[6] strain (RVA/Human-wt/KEN/KCH148/2019/G4P[6]) identified in a stool specimen from a diarrheic child in Kenya. Full genome analysis of strain KCH148 revealed a unique Wa-like genogroup constellation: G4-P[6]-I1-R1-C1-M1-A1-N1-T7-E1-H1. NSP3 genotype T7 is commonly found in porcine rotavirus strains. Furthermore, phylogenetic analysis showed that 10 of the 11 genes of strain KCH148 (VP7, VP4, VP6, VP1-VP3, NSP1, and NSP3-NSP5) appeared to be of porcine origin, the remaining NSP2 gene appearing to be of human origin. Therefore, strain KCH148 was found to have a porcine rotavirus backbone and thus is likely to be of porcine origin. Furthermore, strain KCH148 is assumed to have been derived through interspecies transmission and reassortment events involving porcine and human rotavirus strains. To our knowledge, this is the first report on full genome-based characterization of a human G4P[6] strain from east Africa. Our observations demonstrated the diversity of human G4P[6] strains in Africa, and provide important insights into the origin and evolutionary pattern of zoonotic G4P[6] strains on the African continent.

Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination.

BACKGROUND: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost-benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. METHODS: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. RESULTS: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018-2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. CONCLUSIONS: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.

The Cost and Public Health System Effects of Active Monitoring and Illness Response for Ebola Virus Disease: A Case Evaluation of Georgia.

In August 2014, the World Health Organization declared the Ebola virus disease epidemic in West Africa a public health emergency of international concern. After 2 imported cases of the disease were identified in the United States in autumn 2014, the Centers for Disease Control and Prevention recommended that all jurisdictions begin active monitoring of travelers at risk of developing Ebola virus disease for 21 days from the last day of a potential exposure to minimize the risk of disease transmission. Here we describe the infrastructure development, monitoring processes, total planned expenditures, and effects on the public health system in Georgia associated with active monitoring and illness response of all travelers from Ebola-affected West African countries from October 2014 to March 2016. We conducted qualitative interviews with Georgia Department of Public Health (GDPH) staff. We identified state active monitoring and illness response infrastructure investments and monitoring activities and state and federal funds spent in both areas. And, we evaluated whether active monitoring and illness response enhanced Georgia's ability to respond to future infectious disease outbreaks. Developing the infrastructure to support the monitoring and response required investment in information technology, training of public health and medical personnel, increasing laboratory capacity, and securing personal protective equipment. Estimated total expenditures were $8.25 million, with 76% spent on infrastructure and 17% on daily monitoring. The GDPH leveraged internal resources and partnerships to implement active monitoring and illness response. Infrastructure investment increased surveillance capacity, strengthened relationships between the GDPH and medical providers, and led to the creation of infectious disease transport and hospital networks. Active monitoring and illness response increased outbreak preparedness, but it warrants comparison with other possible responses to determine its overall value.

Assessment of Economic Burden of Concurrent Measles and Rubella Outbreaks, Romania, 2011-2012.

We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies.

Cost-effectiveness of birth-dose hepatitis B vaccination among refugee populations in the African region: a series of case studies.

BACKGROUND: Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country's national immunization policy includes HepB BD. METHODS: We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. RESULTS: Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. CONCLUSIONS: Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Household costs among patients hospitalized with malaria: evidence from a national survey in Malawi, 2012.

BACKGROUND: With 71% of Malawians living on < $1.90 a day, high household costs associated with severe malaria are likely a major economic burden for low income families and may constitute an important barrier to care seeking. Nevertheless, few efforts have been made to examine these costs. This paper describes household costs associated with seeking and receiving inpatient care for malaria in health facilities in Malawi. METHODS: A cross-sectional survey was conducted in a representative nationwide sample of 36 health facilities providing inpatient treatment for malaria from June-August, 2012. Patients admitted at least 12 h before study team visits who had been prescribed an antimalarial after admission were eligible to provide cost information for their malaria episode, including care seeking at previous health facilities. An ingredients-based approach was used to estimate direct costs. Indirect costs were estimated using a human capital approach. Key drivers of total household costs for illness episodes resulting in malaria admission were assessed by fitting a generalized linear model, accounting for clustering at the health facility level. RESULTS: Out of 100 patients who met the eligibility criteria, 80 (80%) provided cost information for their entire illness episode to date and were included: 39% of patients were under 5 years old and 75% had sought care for the malaria episode at other facilities prior to coming to the current facility. Total household costs averaged $17.48 per patient; direct and indirect household costs averaged $7.59 and $9.90, respectively. Facility management type, household distance from the health facility, patient age, high household wealth, and duration of hospital stay were all significant drivers of overall costs. CONCLUSIONS: Although malaria treatment is supposed to be free in public health facilities, households in Malawi still incur high direct and indirect costs for malaria illness episodes that result in hospital admission. Finding ways to minimize the economic burden of inpatient malaria care is crucial to protect households from potentially catastrophic health expenditures.

Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children-Uganda, 2009.

Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs--both financial and nonfinancial--remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary.

Simulations Show Diagnostic Testing For Malaria In Young African Children Can Be Cost-Saving Or Cost-Effective.

Malaria imposes a substantial global disease burden. It disproportionately affects sub-Saharan Africans, particularly young children. In an effort to improve disease management, the World Health Organization (WHO) recommended in 2010 that countries test children younger than age five who present with suspected malaria fever to confirm the diagnosis instead of treating them presumptively with antimalarial drugs. Costs and concerns about the overall health impact of such diagnostic testing for malaria in children remain barriers to full implementation. Using data from national Malaria Indicator Surveys, we estimated two-stage microsimulation models for Angola, Tanzania, and Uganda to assess the policy's cost-effectiveness. We found that diagnostic testing for malaria in children younger than five is cost-saving in Angola. In Tanzania and Uganda the cost per life-year gained is $5.54 and $94.28, respectively. The costs projected for Tanzania and Uganda are less than the WHO standard of $150 per life-year gained. Our results were robust under varying assumptions about cost, prevalence of malaria, and behavior, and they strongly suggest the pursuit of policies that facilitate full implementation of testing for malaria in children younger than five.

Investigating the important correlates of maternal education and childhood malaria infections.

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.

Exploring the impact of targeted distribution of free bed nets on households bed net ownership, socio-economic disparities and childhood malaria infection rates: analysis of national malaria survey data from three sub-Saharan Africa countries.

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.

Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania.

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.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

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.

Use of proxy measures in estimating socioeconomic inequalities in malaria prevalence.

OBJECTIVES: To present and compare socioeconomic status (SES) rankings of households using consumption and an asset-based index as two alternative measures of SES; and to compare and evaluate the performance of these two measures in multivariate analyses of the socioeconomic gradient in malaria prevalence. METHODS: Data for the study come from a survey of 557 households in 25 study villages in Tanzania in 2004. Household SES was determined using consumption and an asset-based index calculated using Principal Components Analysis on a set of household variables. In multivariate analyses of malaria prevalence, we also used two other measures of disease prevalence: parasitaemia and self-report of malaria or fever in the 2 weeks before interview. RESULTS: Household rankings based on the two measures of SES differ substantially. In multivariate analyses, there was a statistically significant negative association between both measures of SES and parasitaemia but not between either measure of SES and self-reported malaria. Age of individual, use of a mosquito net, and wall construction were negatively and significantly associated with parasitaemia, whilst roof construction was positively associated with parasitaemia. Only age remained significant when malaria self-report was used as the measure of disease prevalence. CONCLUSIONS: An asset index is an effective alternative to consumption in measuring the socioeconomic gradient in malaria parasitaemia, but self-report may be an unreliable measure of malaria prevalence for this purpose.

The costs of introducing artemisinin-based combination therapy: evidence from district-wide implementation in rural Tanzania.

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.

Economic burden of malaria in rural Tanzania: variations by socioeconomic status and season.

OBJECTIVE: To determine the economic burden of malaria in a rural Tanzanian setting and identify any differences by socioeconomic status and season. METHODS: Interviews of 557 households in south eastern Tanzania between May and December 2004, on consumption and malaria-related costs. RESULTS: Malaria-related expenses were significantly higher in the dry, non-malarious season than in the rainy season. Households sought treatment more frequently and from more expensive service providers in the dry season, when they have more money. Malaria expenses did not vary significantly across socioeconomic status quintiles, but poorer households spent a higher proportion of their consumption in both seasons. CONCLUSION: Poorer households bear a greater economic burden from malaria relative to their consumption than better-off households. Households are particularly vulnerable to malaria in the rainy season, when malaria prevalence is highest but liquidity is lower. Alternative strategies to assist households to cope with seasonal liquidity issues, including insurance, should be investigated.

Understanding and improving access to prompt and effective malaria treatment and care in rural Tanzania: the ACCESS Programme.

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.