Defining & assessing the quality, usability, and utilization of immunization data.

BACKGROUND: High quality data are needed for decision-making at all levels of the public health system, from guiding public health activities at the local level, to informing national policy development, to monitoring the impact of global initiatives. Although a number of approaches have been developed to evaluate the underlying quality of routinely collected vaccination administrative data, there remains a lack of consensus around how data quality is best defined or measured. DISCUSSION: We present a definitional framework that is intended to disentangle many of the elements that have confused discussions of vaccination data quality to date. The framework describes immunization data in terms of three key characteristics: data quality, data usability, and data utilization. The framework also offers concrete suggestions for a specific set of indicators that could be used to better understand immunization those key characteristics, including Trueness, Concurrence, Relevancy, Efficiency, Completeness, Timeliness, Integrity, Consistency, and Utilization. CONCLUSION: Being deliberate about the choice of indicators; being clear on their definitions, limitations, and methods of measurement; and describing how those indicators work together to give a more comprehensive and practical understanding of immunization data quality, usability, and use, should yield more informed, and therefore better, programmatic decision-making.

Assessment of select electronic health information systems that support immunization data capture - Kenya, 2017.

BACKGROUND: Although electronic health information systems (EHIS) with immunization components exist in Kenya, questions and concerns remain about their use and alignment with the Kenya Ministry of Health's (MOH) National Vaccine and Immunization Program (NVIP). This article reports on the findings of an assessment of select EHIS with immunization components in Kenya, specifically related to system design, development, and implementation. METHODS: We conducted a rapid assessment of select EHIS with immunization components in Kenya from January to May 2017 to understand the design, development, implementation of the EHIS including the lessons learned from their use. We also assessed how the data elements in the EHIS compared to the data elements in the Maternal and Child Health Booklet used in the existing paper based system in Kenya. RESULTS: The EHIS reviewed varied in purpose, content, and population covered. Only one system was built to focus specifically on immunization data. Substantial differences in system functionality and immunization-related data elements included in the EHIS were identified. None of the EHIS had all the data elements necessary to fully replace or operate independently from the standardized paper-based system for recording immunization data in Kenya. CONCLUSIONS: Overall, the findings of this assessment highlighted substantial variation in the EHIS with immunization components. The findings provide insights and lessons learned for the Kenya MOH NVIP, immunization partners, vendors of EHIS, and users of EHIS to consider as Kenya transitions from paper-based to electronic immunization information systems.

Assessing Inactivated Polio Vaccine Introduction and Utilization in Kano State, Nigeria, April-November 2015.

Background: Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Methods: Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). Results: By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). Conclusion: The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions.

Enhancing Workforce Capacity to Improve Vaccination Data Quality, Uganda.

In Uganda, vaccine dose administration data are often not available or are of insufficient quality to optimally plan, monitor, and evaluate program performance. A collaboration of partners aimed to address these key issues by deploying data improvement teams (DITs) to improve data collection, management, analysis, and use in district health offices and health facilities. During November 2014-September 2016, DITs visited all districts and 89% of health facilities in Uganda. DITs identified gaps in awareness and processes, assessed accuracy of data, and provided on-the-job training to strengthen systems and improve healthcare workers' knowledge and skills in data quality. Inaccurate data were observed primarily at the health facility level. Improvements in data management and collection practices were observed, although routine follow-up and accountability will be needed to sustain change. The DIT strategy offers a useful approach to enhancing the quality of health data.

Serological markers for monitoring historical changes in malaria transmission intensity in a highly endemic region of Western Kenya, 1994-2009.

BACKGROUND: Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues. METHODS: This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR. RESULTS: Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial. CONCLUSIONS: In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.

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.

The evolution of pyrimethamine resistant dhfr in Plasmodium falciparum of south-eastern Tanzania: comparing selection under SP alone vs SP+artesunate combination.

BACKGROUND: Sulphadoxine-pyrimethamine (SP) resistance is now widespread throughout east and southern Africa and artemisinin compounds in combination with synthetic drugs (ACT) are recommended as replacement treatments by the World Health Organization (WHO). As well as high cure rates, ACT has been shown to slow the development of resistance to the partner drug in areas of low to moderate transmission. This study looked for evidence of protection of the partner drug in a high transmission African context. The evaluation was part of large combination therapy pilot implementation programme in Tanzania, the Interdisciplinary Monitoring Programme for Antimalarial Combination Therapy (IMPACT-TZ) METHODS: The growth of resistant dhfr in a parasite population where SP Monotherapy was the first-line treatment was measured for four years (2002-2006), and compared with the development of resistant dhfr in a neighbouring population where SP + artesunate (SP+AS) was used as the first-line treatment during the same interval. The effect of the differing treatment regimes on the emergence of resistance was addressed in three ways. First, by looking at the rate of increase in frequency of pre-existing mutant dhfr alleles under monotherapy and combination therapy. Second, by examining whether de-novo mutant alleles emerged under either treatment. Finally, by measuring diversity at three dhfr flanking microsatellite loci upstream of the dhfr gene. RESULTS: The reduction in SP selection pressure resulting from the adoption of ACT slowed the rate of increase in the frequency of the triple mutant resistant dhfr allele. Comparing between the two populations, the higher levels of genetic diversity in sequence flanking the dhfr triple mutant allele in the population where the ACT regimen had been used indicates the reduction in SP selection pressure arising from combination therapy. CONCLUSION: The study demonstrated that, alleles containing two mutations at the dhfr have arisen at least four times independently while those containing triple mutant dhfr arose only once, and were found carrying a single unique Asian-type flanking sequence, which apparently drives the spread of pyrimethamine resistance associated dhfr alleles in east Africa. SP+AS is not recommended for use in areas where SP cure rates are less than 80% but this study reports an observed principle of combination protection from an area where pyrimethamine resistance was already high.

Use of a district health information system 2 routine immunization dashboard for immunization program monitoring and decision making, Kano State, Nigeria.

Introduction: a district health information system 2 tool with a customized routine immunization (RI) module and indicator dashboard was introduced in Kano State, Nigeria, in November 2014 to improve data management and analysis of RI services. We assessed the use of the module for program monitoring and decision-making, as well as the enabling factors and barriers to data collection and use. Methods: a mixed-methods approach was used to assess user experience with the RI data module and dashboard, including 1) a semi-structured survey questionnaire administered at 60 health facilities administering vaccinations and 2) focus group discussions and 16 in-depth interviews conducted with immunization program staff members at the local government area (LGA) and state levels. Results: in health facilities, a RI monitoring chart was used to review progress toward meeting vaccination coverage targets. At the LGA, staff members used RI dashboard data to prioritize health facilities for additional support. At the State level, immunization program staff members use RI data to make policy decisions. They viewed the provision of real-time data through the RI dashboard as a "game changer". Use of immunization data is facilitated through review meetings and supportive supervision visits. Barriers to data use among LGA staff members included inadequate understanding of the data collection tools and computer illiteracy. Conclusion: the routine immunization data dashboard facilitated access to and use of data for decision-making at the LGA, State and national levels, however, use at the health facility level remains limited. Ongoing data review meetings and training on computer skills and data collection tools are recommended.

Targeted Short Message Service-Based Intervention to Improve Routine Immunization Reporting in Bauchi State, Nigeria, 2016.

Introduction: High quality, timely and complete immunization data are essential for program planning and decision-making. In Nigeria, the National Health Management Information System (NHMIS) Routine Immunization (RI) module and dashboard (on the District Health Information System version 2 (DHIS2) platform) support the use of real time RI data. We deployed an automated short message service (SMS) notification system that works with the existing RI module to facilitate improvements in RI data in the DHIS2. Methods: A pilot project was performed using intervention and control local government areas (LGAs). A mixed methods approach using both qualitative and quantitative methods was used to evaluate the system. We assessed changes in reporting rates across different reports. The evaluation also included baseline and post-intervention surveys of health facility (HF) staff. Results: Reporting timeliness (76% pre and 99% post intervention) and completeness (83% pre and 99% post intervention) were consistently higher during the post-intervention than the pre-intervention period for facilities in the intervention LGA while reporting timeliness (65% pre and 66% post intervention) and completeness (71% and 77% post intervention) for facilities in the control LGA showed no change. Users reported that the SMS system was easy to understand and helped to facilitate improvements in consistency of data and timeliness of reporting. Inability of health care workers to effect changes at the HF level and the lack of immediate feedback were reported as key challenges to timeliness and quality of reports. Conclusion: An SMS-based intervention improved timeliness and completeness of health data reporting. However, the intervention should be evaluated on a larger scale over a longer time period before considering a national implementation.

Association of Malnutrition with Subsequent Malaria Parasitemia among Children Younger than Three years in Kenya: A Secondary Data Analysis of the Asembo Bay Cohort Study.

Malaria and malnutrition remain primary causes of morbidity and mortality among children younger than 5 years in Africa. Studies investigating the association between malnutrition and subsequent malaria outcomes are inconsistent. We studied the effects of malnutrition on incidence and prevalence of malaria parasitemia in data from a cohort studied in the 1990s. Data came from the Asembo Bay cohort study, which collected malaria and health information on children from 1992 to 1996 in western Kenya. Infants were enrolled at birth and followed up until loss to follow-up, death, end of study, or 5 years old. Anthropometric measures and blood specimens were obtained monthly. Nutritional exposures included categorized Z-scores for height-for-age, weight-for-age, and weight-for-height. Febrile parasitemia and afebrile parasitemia were assessed with thick and thin blood films. Multiply imputed and weighted multinomial generalized estimating equation models estimated odds ratios (OR) for the association between exposures and outcomes. The sample included 1,182 children aged 0-30 months who contributed 18,028 follow-up visits. There was no significant association between malnutrition and either incident febrile parasitemia or prevalent febrile parasitemia. Prevalence ORs for afebrile parasitemia increased from 1.07 (95% CI: 0.89, 1.29) to 1.35 (1.03, 1.76) as stunting severity increased from mild to severe, and from 1.16 (1.02, 1.33) to 1.35 (1.09, 1.66) as underweight increased from mild to moderate. Stunting and underweight did not show a significant association with subsequent febrile parasitemia infections, but they did show a modest association with subsequent afebrile parasitemia. Consideration should be given to testing malnourished children for malaria, even if they present without fever.

Drug coverage in treatment of malaria and the consequences for resistance evolution--evidence from the use of sulphadoxine/pyrimethamine.

BACKGROUND: It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes. METHODS: To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared. RESULTS: The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N) allele (conferring pyrimethamine resistance) increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance) increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP. CONCLUSION: The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial impact on drug pressure. The selection applied by first-line use is strong enough to overcome recombination pressure and create significant linkage disequilibrium between the unlinked genetic determinants of pyrimethamine and sulphadoxine resistance, showing that recombination is no barrier to the emergence of resistance to combination treatments when they are used as the first-line malaria therapy.

Financial cost analysis of a strategy to improve the quality of administrative vaccination data in Uganda.

BACKGROUND: High-quality vaccination data are critical to planning, implementation and evaluation of immunization programs. However, sub-optimal administrative vaccination data quality in low- and middle-income countries persist for heterogeneous reasons, though most relate to organizational factors and human behavior. The nationwide Data Improvement Team (DIT) strategy in Uganda aimed to strengthen human resource capacity to generate quality administrative vaccination data at the health facility. METHODS: A financial cost analysis of the Uganda DIT strategy (2014-2016) was conducted from the program funder perspective. Activity-based micro-costing from funder financial and program monitoring records was used to estimate total and unit costs by program area (in 2016 US dollars). Hypothetical scenarios were developed to illustrate potential approaches to reducing costs. RESULTS: Over 25 months the DIT strategy was implemented in all 116 operational districts and 3443 (89%) health facilities in Uganda at a total financial cost of US $575 275. Training and deployment of DITs accounted for the highest proportion of expenditure across program areas (69%). Transport, per diems, lodging, and honoraria for DIT members and national supervisors were the main cost drivers of the strategy. Deployment of 557 DIT members cost US $839 per DIT member, US $4 030 per district, and US $136 per health facility. The estimated opportunity cost of government staff time wasn't a major cost driver (2.5%) of total cost. CONCLUSION: The results provide the first estimates of the magnitude and drivers of cost to implement a national workforce capacity building strategy to improve administrative vaccination data quality in a low- or middle-income country. Financial costs are a critical input to combine with future outcome data to describe the cost of strategies relative to performance outcomes. The operational costs of the strategy were modest (0.5-1.6%) relative to the estimated operational costs of Uganda's national immunization program.

Implementing the routine immunisation data module and dashboard of DHIS2 in Nigeria, 2014-2019.

In 2010, Nigeria adopted the use of web-based software District Health Information System, V.2 (DHIS2) as the platform for the National Health Management Information System. The platform supports real-time data reporting and promotes government ownership and accountability. To strengthen its routine immunisation (RI) component, the US Centers for Disease Control and Prevention (CDC) through its implementing partner, the African Field Epidemiology Network-National Stop Transmission of Polio, in collaboration with the Government of Nigeria, developed the RI module and dashboard and piloted it in Kano state in 2014. The module was scaled up nationally over the next 4 years with funding from the Bill & Melinda Gates Foundation and CDC. One implementation officer was deployed per state for 2 years to support operations. Over 60 000 RI healthcare workers were trained on data collection, entry and interpretation and each local immunisation officer in the 774 local government areas (LGAs) received a laptop and stock of RI paper data tools. Templates for national-level and state-level RI bulletins and LGA quarterly performance tools were developed to promote real-time data use for feedback and decision making, and enhance the performance of RI services. By December 2017, the DHIS2 RI module had been rolled out in all 36 states and the Federal Capital Territory, and all states now report their RI data through the RI Module. All states identified at least one government DHIS2 focal person for oversight of the system's reporting and management operations. Government officials routinely collect RI data and use them to improve RI vaccination coverage. This article describes the implementation process-including planning and implementation activities, achievements, lessons learnt, challenges and innovative solutions-and reports the achievements in improving timeliness and completeness rates.

Concentration and drug prices in the retail market for malaria treatment in rural Tanzania.

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.

Developing standardized competencies to strengthen immunization systems and workforce.

Despite global support for immunization as a core component of the human right to health and the maturity of immunization programs in low- and middle-income countries throughout the world, there is no comprehensive description of the standardized competencies needed for immunization programs at the national, multiple sub-national, and community levels. The lack of defined and standardized competencies means countries have few guidelines to help them address immunization workforce planning, program management, and performance monitoring. Potential consequences resulting from the lack of defined competencies include inadequate or inefficient distribution of resources to support the required functions and difficulties in adequately managing the health workforce. In 2015, an international multi-agency working group convened to define standardized competencies that national immunization programs could adapt for their own workforce planning needs. The working group used a stepwise approach to ensure that the competencies would align with immunization programs' objectives. The first step defined the attributes of a successful immunization program. The group then defined the work functions needed to achieve those attributes. Based on the work functions, the working group defined specific competencies. This process resulted in three products: (1) Attributes of an immunization program described within eight technical domains at four levels within a health system: National, Provincial, District/Local, and Community; (2) 229 distinct functions within those eight domains at each of the four levels; and (3) 242 competencies, representing eight technical domains and two foundational domains (Management and Leadership and Vaccine Preventable Diseases and Program). Currently available as a working draft and being tested with immunization projects in several countries, the final document will be published by WHO as normative guidelines. Vertical immunization programs as well as integrated systems can customize the framework to suit their needs. Standardized competencies can support immunization program improvements and help strengthen effective health systems.

dhfr and dhps genotype and sulfadoxine-pyrimethamine treatment failure in children with falciparum malaria in the Democratic Republic of Congo.

OBJECTIVE: To determine the relationship between mutations in dhfr and dhps and SP treatment failure in Plasmodium falciparum malaria in the Democratic Republic of the Congo (DRC). METHODS: Therapeutic efficacy trial was conducted in Rutshuru, Eastern DRC, between June and September 2002, comparing sulfadoxine-pyrimethamine (SP), SP plus amodiaquine (AQSP) and artesunate plus SP (ASSP) regimens for treating malaria in children under 5 years old. We genotyped 212 samples for mutations associated with SP resistance and investigated their association with treatment failure. RESULTS: In the SP arm, 61% of the subjects experienced treatment failure after 14 days. The failure rate was lower in the combination arms (AQSP: 32%, ASSP: 21%). The dhfr-108 and dhfr-51 mutations were nearly universal while 89% of the samples had at least one additional mutation at dhfr-59, dhps-437 or dhps-540. Dhps mutations had a bigger impact on treatment failure in children with high parasite density: for children with a parasite density <45 000 parasites/microl, the risk of treatment failure was 37% for mutations at dhps-437 and dhps-540 mutation and 21% for neither mutation [risk difference (RD) = 17%, 95% CI: -3%, 36%]. In children with a parasite density >45 000 parasites/microl, the treatment failure risk was 58% and 8% for children with both mutations or neither mutation, respectively (RD = 51%, 95% CI: 34%, 67%). CONCLUSIONS: Dhps-437 and dhps-540 are strongly associated with SP treatment failure and should be evaluated further as a method for surveillance of SP-based therapy in DRC.

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.

Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients--Tanzania, 2005.

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.

Malaria in pregnant women in an area with sustained high coverage of insecticide-treated bed nets.

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.