Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies.

The emergence and spread of artemisinin-resistant Plasmodium falciparum is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the Pfkelch13 gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the Pfkelch13 propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin-exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the Pfkelch13 propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of Pfkelch13 polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various Pfkelch13 mutations have been selected under artemisinin pressure.

Patient adherence to prescribed artemisinin-based combination therapy in Garissa County, Kenya, after three years of health care in a conflict setting.

BACKGROUND: Current day malaria cases and deaths are indicative of a lack of access to both methods of prevention, diagnosis, and treatment; an important determinant of treatment efficacy is adherence. This study is a follow up to the baseline study of adherence to artemether-lumefantrine (AL) carried out in Garissa District in 2010. The study presented evaluates any changes in adherence levels which may have occurred in the area during this period and after nearly three years of sustained use of ACT across the public health sector. METHODS: The study was carried out in Garissa County in the North Eastern Province of Kenya and included patients fitting the suspected malaria case definition and having been prescribed AL, regardless of confirmatory diagnosis. A questionnaire assessed the intake of AL via both self-reporting by the participant and observation of blister packs by the interviewer. On separate occasions exit interviews with patients and observations of prescribers were also carried out. RESULTS: Of the 218 participants enrolled, 195 were successfully followed up. 60% of participants were found to be adherent to the three-day AL regimen, this is 4.7% lower than the proportion of participants adherent in 2010; the result of a two-sided z-test was not significant (p = 0.23). The odds of the patient being adherent to AL increased by 65% with each additional correct statement regarding how to take AL that a patient could recall (between zero and four statements), this was the only variable significantly associated with patient adherence (p = 0.01). CONCLUSION: Sustaining the ACT adherence rates at the 2010 levels, through 2.5 years of insecurity in the study area is an achievement and suggests that if security can be improved barriers to improving health service quality and patient adherence to AL would be removed. This study, by looking specifically at anti-malarial adherence over a prolonged period and in a setting of severe conflict, provides a valuable and rare insight in to the challenges and barriers to ACT adherence in such settings.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children aged less than five years: results of an open-label, randomized, single-centre study.

BACKGROUND: This open-label, randomized study evaluated efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in treatment of uncomplicated falciparum malaria in children below five years of age, to build evidence on use of AL as first-line treatment and DP as second-line treatment in Kenya. METHODS: A total of 454 children aged six to 59 months with uncomplicated falciparum malaria were randomized (1:1) to receive AL dispersible or DP paediatric tablets and followed up for 42 days. Primary efficacy variable was corrected adequate clinical and parasitological response (ACPR) rate on day 28. Secondary variables included corrected (day 14, 28 and 42), uncorrected (day 3, 14, 28 and 42) cure rates, parasitological failure at days 3, 14 and 42. Acceptability and tolerability of both drugs were assessed by caregiver questionnaire. RESULTS: On day 28, corrected ACPR rates for AL dispersible and DP paediatric were 97.8% (95% CI: 94.9-99.3) and 99.1% (95% CI: 96.8-99.9), respectively, in intention-to-treat population, with no significant treatment differences noted between AL dispersible and DP paediatric arms. Additionally, no significant differences were observed for PCR corrected cure rates on days 14 and ACPR on day 42 for AL dispersible (100%; 96.8%) and DP paediatric (100%; 98.7%). Similarly, for PCR uncorrected cure rates, no significant differences were seen on days 3, 14, 28, and 42 for AL dispersible (99.1%; 98.7%; 81.1%; 67.8%) and DP paediatric (100%; 100%; 87.7%; 70.5%). Parasite clearance was rapid, with approximately 90% clearance achieved in 40 hours in both treatment arms. Incidence of adverse events was related to underlying disease; malaria being reported in both treatment arms. One serious adverse event was noted in AL dispersible (0.42%) arm, not related to study drug. Adherence to treatment regimen was higher for children treated with AL dispersible (93.6%) compared to DP paediatric (85.6%). Acceptability of AL dispersible regimen was assessed as being significantly better than DP paediatric. CONCLUSIONS: AL and DP were both efficacious and well tolerated, and had similar effects at day 42 on risk of recurrent malaria. No signs of Plasmodium falciparum tolerance to artemisinins were noted. TRIAL REGISTRATION: PACTR201111000316370.

Symptomatic malaria diagnosis overestimate malaria prevalence, but underestimate anaemia burdens in children: results of a follow up study in Kenya.

BACKGROUND: The commonly accepted gold standard diagnostic method for detecting malaria is a microscopic reading of Giemsa-stained blood films. However, symptomatic diagnosis remains the basis of therapeutic care for the majority of febrile patients in malaria endemic areas. This study aims to compare the discrepancy in malaria and anaemia burdens between symptomatic diagnosed patients with those diagnosed through the laboratory. METHODS: Data were collected from Western Kenya during a follow-up study of 887 children with suspected cases of malaria visiting the health facilities. In the laboratory, blood samples were analysed for malaria parasite and haemoglobin levels. Differences in malaria prevalence between symptomatic diagnosis and laboratory diagnosis were analysed by Chi-square test. Bayesian probabilities were used for the approximation of the malaria and anaemia burdens. Regression analysis was applied to: (1) determine the relationships between haemoglobin levels, and malaria parasite density and (2) relate the prevalence of anaemia and the prevalence of malaria. RESULTS: The prevalence of malaria and anaemia ranged from 10% to 34%, being highest during the rainy seasons. The predominant malaria parasite was P. falciparum (92.3%), which occurred in higher density in children aged 2‒5 years. Fever, high temperature, sweating, shivering, vomiting and severe headache symptoms were associated with malaria during presumptive diagnosis. After conducting laboratory diagnosis, lower malaria prevalence was reported among the presumptively diagnosed patients. Surprisingly, there were no attempts to detect anaemia in the same cohort. There was a significant negative correlation between Hb levels and parasite density. We also found a positive correlation between the prevalence of anaemia and the prevalence of malaria after laboratory diagnosis indicating possible co-occurrence of malaria and anaemia. CONCLUSION: Symptomatic diagnosis of malaria overestimates malaria prevalence, but underestimates the anaemia burden in children. Good clinical practice dictates that a laboratory should confirm the presence of parasites for all suspected cases of malaria.

A systematic review of health technology assessment tools in sub-Saharan Africa: methodological issues and implications.

BACKGROUND: Health technology assessment (HTA) is mostly used in the context of high- and middle-income countries. Many "resource-poor" settings, which have the greatest need for critical assessment of health technology, have a limited basis for making evidence-based choices. This can lead to inappropriate use of technologies, a problem that could be addressed by HTA that enables the efficient use of resources, which is especially crucial in such settings. There is a lack of clarity about which HTA tools should be used in these settings. This research aims to provide an overview of proposed HTA tools for "resource-poor" settings with a specific focus on sub-Saharan Africa (SSA). METHODOLOGY: A systematic review was conducted using basic steps from the PRISMA guidelines. Studies that described HTA tools applicable for "resource-limited" settings were identified and critically appraised. Only papers published between 2003 and 2013 were included. The identified tools were assessed according to a checklist with methodological criteria. RESULTS: Six appropriate tools that are applicable in the SSA setting and cover methodological robustness and ease of use were included in the review. Several tools fulfil these criteria, such as the KNOW ESSENTIALS tool, Mini-HTA tool, and Multi-Criteria Decision Analysis but their application in the SSA context remains limited. The WHO CHOICE method is a standardized decision making tool for choosing interventions but is limited to their cost-effectiveness. Most evaluation of health technology in SSA focuses on priority setting. There is a lack of HTA tools that can be used for the systematic assessment of technology in the SSA context. CONCLUSIONS: An appropriate HTA tool for "resource-constrained" settings, and especially SSA, should address all important criteria of decision making. By combining the two most promising tools, KNOW ESSENTIALS and Multi-Criteria Decision Analysis, appropriate analysis of evidence with a robust and flexible methodology could be applied for the SSA setting.

Molecular epidemiology of geographically dispersed Vibrio cholerae, Kenya, January 2009-May 2010.

Numerous outbreaks of cholera have occurred in Kenya since 1971. To more fully understand the epidemiology of cholera in Kenya, we analyzed the genetic relationships among 170 Vibrio cholerae O1 isolates at 5 loci containing variable tandem repeats. The isolates were collected during January 2009-May 2010 from various geographic areas throughout the country. The isolates grouped genetically into 5 clonal complexes, each comprising a series of genotypes that differed by an allelic change at a single locus. No obvious correlation between the geographic locations of the isolates and their genotypes was observed. Nevertheless, geographic differentiation of the clonal complexes occurred. Our analyses showed that multiple genetic lineages of V. cholerae were simultaneously infecting persons in Kenya. This finding is consistent with the simultaneous emergence of multiple distinct genetic lineages of V. cholerae from endemic environmental reservoirs rather than recent introduction and spread by travelers.

The effect of mobile phone text-message reminders on Kenyan health workers' adherence to malaria treatment guidelines: a cluster randomised trial.

BACKGROUND: Health workers' malaria case-management practices often differ from national guidelines. We assessed whether text-message reminders sent to health workers' mobile phones could improve and maintain their adherence to treatment guidelines for outpatient paediatric malaria in Kenya. METHODS: From March 6, 2009, to May 31, 2010, we did a cluster-randomised controlled trial at 107 rural health facilities in 11 districts in coastal and western Kenya. With a computer-generated sequence, health facilities were randomly allocated to either the intervention group, in which all health workers received text messages on their personal mobile phones on malaria case-management for 6 months, or the control group, in which health workers did not receive any text messages. Health workers were not masked to the intervention, although patients were unaware of whether they were in an intervention or control facility. The primary outcome was correct management with artemether-lumefantrine, defined as a dichotomous composite indicator of treatment, dispensing, and counselling tasks concordant with Kenyan national guidelines. The primary analysis was by intention to treat. The trial is registered with Current Controlled Trials, ISRCTN72328636. FINDINGS: 119 health workers received the intervention. Case-management practices were assessed for 2269 children who needed treatment (1157 in the intervention group and 1112 in the control group). Intention-to-treat analysis showed that correct artemether-lumefantrine management improved by 23·7 percentage-points (95% CI 7·6-40·0; p=0·004) immediately after intervention and by 24·5 percentage-points (8·1-41·0; p=0·003) 6 months later. INTERPRETATION: In resource-limited settings, malaria control programmes should consider use of text messaging to improve health workers' case-management practices. FUNDING: The Wellcome Trust.

Factors associated with utilization of community health workers in improving access to malaria treatment among children in Kenya.

BACKGROUND: The success of community case management in improving access to effective malaria treatment for young children relies on broad utilization of community health workers (CHWs) to diagnose and treat fever cases. A better understanding of the factors associated with CHW utilization is crucial in informing national malaria control policy and strategy in Kenya. Specifically, little is known in Kenya on the extent to which CHWs are utilized, the characteristics of families who report utilizing CHWs and whether utilization is associated with improved access to prompt and effective malaria treatment. This paper examines factors associated with utilization of CHWs in improving access to malaria treatment among children under five years of age by women caregivers in two malaria endemic districts in Kenya. METHODS: This study was conducted in 113 hard-to-reach and poor villages in Malindi and Lamu districts in the coastal region classified as having endemic transmission of malaria. A cross-sectional household survey was conducted using a standardized malaria indicator questionnaire at baseline (n=1,187) and one year later at endline assessment (n=1,374) using two-stage cluster sampling. RESULTS: There was an increase in reported utilization of CHWs as source of advice/treatment for child fevers from 2% at baseline to 35% at endline, accompanied by a decline in care-seeking from government facilities (from 67% to 48%) and other sources (26% to 2%) including shops. The most poor households and poor households reported higher utilization of CHWs at 39.4% and 37.9% respectively, compared to the least poor households (17.0%). Households in villages with less than 200 households reported higher CHWs utilization as compared to households in villages having >200 households. Prompt access to timely and effective treatment was 5.7 times higher (95% CI 3.4-9.7) when CHWs were the source of care sought. Adherence was high regardless of whether source was CHWs (73.1%) or public health facility (66.7%). CONCLUSIONS: The potential for utilization of CHWs in improving access to malaria treatment at the community level is promising. This will not only enhance access to treatment by the poorest households but also provide early and appropriate treatment to vulnerable individuals, especially those living in hard to reach areas.

Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems.

BACKGROUND: Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of Anopheles vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics. METHODS: Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with Plasmodium falciparum determined. RESULTS: Prevalence of febrile illness with P. falciparum was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of Anopheles arabiensis, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of A. arabiensis adult females were infected with P. falciparum sporozoites in the rainy season. CONCLUSIONS: Malaria in Kakuma refugee camp was due mainly to infection with P. falciparum and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by A. arabiensis, whose populations were facilitated by installation of man-made water distribution and catchment systems.

Bed net ownership in Kenya: the impact of 3.4 million free bed nets.

BACKGROUND: In July and September 2006, 3.4 million long-lasting insecticide-treated bed nets (LLINs) were distributed free in a campaign targeting children 0-59 months old (CU5s) in the 46 districts with malaria in Kenya. A survey was conducted one month after the distribution to evaluate who received campaign LLINs, who owned insecticide-treated bed nets and other bed nets received through other channels, and how these nets were being used. The feasibility of a distribution strategy aimed at a high-risk target group to meet bed net ownership and usage targets is evaluated. METHODS: A stratified, two-stage cluster survey sampled districts and enumeration areas with probability proportional to size. Handheld computers (PDAs) with attached global positioning systems (GPS) were used to develop the sampling frame, guide interviewers back to chosen households, and collect survey data. RESULTS: In targeted areas, 67.5% (95% CI: 64.6, 70.3%) of all households with CU5s received campaign LLINs. Including previously owned nets, 74.4% (95% CI: 71.8, 77.0%) of all households with CU5s had an ITN. Over half of CU5s (51.7%, 95% CI: 48.8, 54.7%) slept under an ITN during the previous evening. Nearly forty percent (39.1%) of all households received a campaign net, elevating overall household ownership of ITNs to 50.7% (95% CI: 48.4, 52.9%). CONCLUSIONS: The campaign was successful in reaching the target population, families with CU5s, the risk group most vulnerable to malaria. Targeted distribution strategies will help Kenya approach indicator targets, but will need to be combined with other strategies to achieve desired population coverage levels.

Importance of strategic management in the implementation of private medicine retailer programmes: case studies from three districts in Kenya.

BACKGROUND: The home-management of malaria strategy seeks to improve prompt and effective anti-malarial drug use through the informal sector, with a potential channel being the Private Medicine Retailers (PMRs). Previous evaluations of PMR programmes focused on their impact on retailer knowledge and practices, with limited evidence about the influence of implementation processes on the impacts at scale. This paper examines how the implementation processes of three PMR programmes in Kenya, each scaled up within a district, contributed to the outcomes observed. These were a Ministry of Health programme in Kwale district; and two programmes supported by non-governmental organizations in collaboration with government in Kisii Central and Bungoma districts. METHODS: The research methods included 24 focus group discussions with clients and PMRs, 19 in-depth interviews with implementing actors, document review and a diary of events. The data were analysed using the combination of a broad policy analysis framework and more specific scaling up/diffusion of innovations frameworks. RESULTS: The Kisii programme, a case study of successful implementation, was underpinned by good relationships between district health managers and a "resource team", supported by a memorandum of understanding which enabled successful implementation. It had flexible budgetary and decision making processes which were responsive to local contexts, and took account of local socio-economic activities. In contrast, the Kwale programme, which had implementation challenges, was characterised by a complex funding process, with lengthy timelines, that was tied to the government financial management system which constrained implementation Although there was a flexible funding system in Bungoma, a perceived lack of transparency in fund management, inadequate management of inter-organisational relationships, and inability to adapt and respond to changing circumstances led to implementation difficulties. CONCLUSIONS: For effective scaling up of PMR programmes, the provision of technical support and adequate resources are vital, but not sufficient on their own. An active strategy to manage relationships between implementing actors through effective communication mechanisms is essential. Successful outcomes may be realised if a strong and transparent management system, including management of financial resources, is put in place. This study provides evidence of the value of assessing implementation processes as part of impact evaluation for public health programmes.

Possible interruption of malaria transmission, highland Kenya, 2007-2008.

Highland areas where malaria transmission is unstable are targets for malaria elimination because transmission decreases to low levels during the dry season. In highland areas of Kipsamoite and Kapsisiywa, Kenya (population approximately 7,400 persons), annual household indoor residual spraying with a synthetic pyrethroid was performed starting in 2005, and artemether/lumefantrine was implemented as first-line malaria treatment in October 2006. During April 2007-March 2008, no microscopy-confirmed cases of malaria occurred at the sites. In 4 assessments of asymptomatic persons during May 2007-April 2008, a total of <0.3% of persons were positive for asexual Plasmodium falciparum by microscopy or PCR at any time, and none were positive by PCR at the last 2 sample collections. Our findings show that in such areas, interruption and eventual elimination of malaria transmission may be achievable with widespread annual indoor residual spraying of households and artemisinin combination therapy.

Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa.

OBJECTIVES: Resistance to pyrimethamine in Plasmodium falciparum is conferred by mutations in the gene encoding dihydrofolate reductase (DHFR). It is known that DHFR double mutants have evolved independently in multiple geographic areas, whereas the triple mutant prevalent in Africa appears to have originated in south-east Asia. In this study, we investigated whether other triple mutants may have evolved independently in Africa. METHODS: We determined the DHFR genotypes and haplotypes of five microsatellite loci flanking the DHFR locus between 4.49 kb upstream and 1.48 kb downstream of 159 isolates collected from three African countries (Republic of Congo, Ghana and Kenya). RESULTS: The CIRNI type of DHFR triple mutant (with mutations underlined at amino acid positions 51, 59 and 108) was predominant in the Republic of Congo (82%) and Ghana (81%) and was the second most prevalent in Kenya (27%), where the CICNI type of DHFR double mutant was dominant. Three distinct microsatellite haplotypes were identified in the DHFR triple mutant. One haplotype was identical to that originating in south-east Asia. The other two haplotypes occurred in Ghana and Kenya, which were unique, previously undescribed and identical to those of the two DHFR double mutants found in the same locations. CONCLUSIONS: This study presents strong evidence for the unique, multiple independent evolution of pyrimethamine resistance in Africa. Indigenous evolution of the triple mutant from the double mutant appears to have occurred in a step-wise manner in Kenya and Ghana or in nearby countries in east and west Africa.

Reviewing the literature on access to prompt and effective malaria treatment in Kenya: implications for meeting the Abuja targets.

BACKGROUND: Effective case management is central to reducing malaria mortality and morbidity worldwide, but only a minority of those affected by malaria, have access to prompt effective treatment.In Kenya, the Division of Malaria Control is committed to ensuring that 80 percent of childhood fevers are treated with effective anti-malarial medicines within 24 hours of fever onset, but this target is largely unmet. This review aimed to document evidence on access to effective malaria treatment in Kenya, identify factors that influence access, and make recommendations on how to improve prompt access to effective malaria treatment. Since treatment-seeking patterns for malaria are similar in many settings in sub-Saharan Africa, the findings presented in this review have important lessons for other malaria endemic countries. METHODS: Internet searches were conducted in PUBMED (MEDLINE) and HINARI databases using specific search terms and strategies. Grey literature was obtained by soliciting reports from individual researchers working in the treatment-seeking field, from websites of major organizations involved in malaria control and from international reports. RESULTS: The review indicated that malaria treatment-seeking occurs mostly in the informal sector; that most fevers are treated, but treatment is often ineffective. Irrational drug use was identified as a problem in most studies, but determinants of this behaviour were not documented. Availability of non-recommended medicines over-the-counter and the presence of substandard anti-malarials in the market are well documented. Demand side determinants of access include perception of illness causes, severity and timing of treatment, perceptions of treatment efficacy, simplicity of regimens and ability to pay. Supply side determinants include distance to health facilities, availability of medicines, prescribing and dispensing practices and quality of medicines. Policy level factors are around the complexity and unclear messages regarding drug policy changes. CONCLUSION: Kenya, like many other African countries, is still far from achieving the Abuja targets. The government, with support from donors, should invest adequately in mechanisms that promote access to effective treatment. Such approaches should focus on factors influencing multiple dimensions of access and will require the cooperation of all stakeholders working in malaria control.

Effect of expanded insecticide-treated bednet coverage on child survival in rural Kenya: a longitudinal study.

BACKGROUND: The potential of insecticide-treated bednets (ITNs) to contribute to child survival has been well documented in randomised controlled trials. ITN coverage has increased rapidly in Kenya from 7% in 2004 to 67% in 2006. We aimed to assess the extent to which this investment has led to improvements in child survival. METHODS: A dynamic cohort of about 3500 children aged 1-59 months were enumerated three times at yearly intervals in 72 rural clusters located in four districts of Kenya. The effect of ITN use on mortality was assessed with Poisson regression to take account of potential effect-modifying and confounding covariates. FINDINGS: 100 children died over 2 years. Overall mortality rates were much the same in the first and second years of the study (14.5 per 1000 person-years in the first year and 15.4 per 1000 person-years in the second). After adjustment for age, time period, and a number of other possible confounding variables, ITN use was associated with a 44% reduction in mortality (mortality rate ratio 0.56, 95% CI 0.33-0.96; p=0.04). This level of protection corresponds to about seven deaths averted for every 1000 ITNs distributed. INTERPRETATION: A combined approach of social marketing followed by mass free distribution of ITNs translated into child survival effects that are comparable with those seen in previous randomised controlled trials.

A randomized, open-label, comparative efficacy trial of artemether-lumefantrine suspension versus artemether-lumefantrine tablets for treatment of uncomplicated Plasmodium falciparum malaria in children in western Kenya.

BACKGROUND: Artemether/lumefantrine (AL) has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets. METHODS: A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6-59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem) or three-dose of artemether/lumefantrine suspension (Co-artesiane) for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days. RESULTS: Ninety three percent (124/133) and 90% (121/134) children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events. CONCLUSION: The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane(R)) was not superior to six-dose artemether-lumefantrine tablets (Coartem) for the treatment of uncomplicated malaria in children below five years of age in western Kenya.

Costs and cost-effectiveness of delivering intermittent preventive treatment through schools in western Kenya.

BACKGROUND: Awareness of the potential impact of malaria among school-age children has stimulated investigation into malaria interventions that can be delivered through schools. However, little evidence is available on the costs and cost-effectiveness of intervention options. This paper evaluates the costs and cost-effectiveness of intermittent preventive treatment (IPT) as delivered by teachers in schools in western Kenya. METHODS: Information on actual drug and non-drug associated costs were collected from expenditure and salary records, government budgets and interviews with key district and national officials. Effectiveness data were derived from a cluster-randomised-controlled trial of IPT where a single dose of sulphadoxine-pyrimethamine and three daily doses of amodiaquine were provided three times in year (once termly). Both financial and economic costs were estimated from a provider perspective, and effectiveness was estimated in terms of anaemia cases averted. A sensitivity analysis was conducted to assess the impact of key assumptions on estimated cost-effectiveness. RESULTS: The delivery of IPT by teachers was estimated to cost US$ 1.88 per child treated per year, with drug and teacher training costs constituting the largest cost components. Set-up costs accounted for 13.2% of overall costs (equivalent to US$ 0.25 per child) whilst recurrent costs accounted for 86.8% (US$ 1.63 per child per year). The estimated cost per anaemia case averted was US$ 29.84 and the cost per case of Plasmodium falciparum parasitaemia averted was US$ 5.36, respectively. The cost per case of anaemia averted ranged between US$ 24.60 and 40.32 when the prices of antimalarial drugs and delivery costs were varied. Cost-effectiveness was most influenced by effectiveness of IPT and the background prevalence of anaemia. In settings where 30% and 50% of schoolchildren were anaemic, cost-effectiveness ratios were US$ 12.53 and 7.52, respectively. CONCLUSION: This study provides the first evidence that IPT administered by teachers is a cost-effective school-based malaria intervention and merits investigation in other settings.

The impact of routine data quality assessments on electronic medical record data quality in Kenya.

BACKGROUND: Routine Data Quality Assessments (RDQAs) were developed to measure and improve facility-level electronic medical record (EMR) data quality. We assessed if RDQAs were associated with improvements in data quality in KenyaEMR, an HIV care and treatment EMR used at 341 facilities in Kenya. METHODS: RDQAs assess data quality by comparing information recorded in paper records to KenyaEMR. RDQAs are conducted during a one-day site visit, where approximately 100 records are randomly selected and 24 data elements are reviewed to assess data completeness and concordance. Results are immediately provided to facility staff and action plans are developed for data quality improvement. For facilities that had received more than one RDQA (baseline and follow-up), we used generalized estimating equation models to determine if data completeness or concordance improved from the baseline to the follow-up RDQAs. RESULTS: 27 facilities received two RDQAs and were included in the analysis, with 2369 and 2355 records reviewed from baseline and follow-up RDQAs, respectively. The frequency of missing data in KenyaEMR declined from the baseline (31% missing) to the follow-up (13% missing) RDQAs. After adjusting for facility characteristics, records from follow-up RDQAs had 0.43-times the risk (95% CI: 0.32-0.58) of having at least one missing value among nine required data elements compared to records from baseline RDQAs. Using a scale with one point awarded for each of 20 data elements with concordant values in paper records and KenyaEMR, we found that data concordance improved from baseline (11.9/20) to follow-up (13.6/20) RDQAs, with the mean concordance score increasing by 1.79 (95% CI: 0.25-3.33). CONCLUSIONS: This manuscript demonstrates that RDQAs can be implemented on a large scale and used to identify EMR data quality problems. RDQAs were associated with meaningful improvements in data quality and could be adapted for implementation in other settings.

Increasing coverage and decreasing inequity in insecticide-treated bed net use among rural Kenyan children.

BACKGROUND: Inexpensive and efficacious interventions that avert childhood deaths in sub-Saharan Africa have failed to reach effective coverage, especially among the poorest rural sectors. One particular example is insecticide-treated bed nets (ITNs). In this study, we present repeat observations of ITN coverage among rural Kenyan homesteads exposed at different times to a range of delivery models, and assess changes in coverage across socioeconomic groups. METHODS AND FINDINGS: We undertook a study of annual changes in ITN coverage among a cohort of 3,700 children aged 0-4 y in four districts of Kenya (Bondo, Greater Kisii, Kwale, and Makueni) annually between 2004 and 2006. Cross-sectional surveys of ITN coverage were undertaken coincidentally with the incremental availability of commercial sector nets (2004), the introduction of heavily subsidized nets through clinics (2005), and the introduction of free mass distributed ITNs (2006). The changing prevalence of ITN coverage was examined with special reference to the degree of equity in each delivery approach. ITN coverage was only 7.1% in 2004 when the predominant source of nets was the commercial retail sector. By the end of 2005, following the expansion of heavily subsidized clinic distribution system, ITN coverage rose to 23.5%. In 2006 a large-scale mass distribution of ITNs was mounted providing nets free of charge to children, resulting in a dramatic increase in ITN coverage to 67.3%. With each subsequent survey socioeconomic inequity in net coverage sequentially decreased: 2004 (most poor [2.9%] versus least poor [15.6%]; concentration index 0.281); 2005 (most poor [17.5%] versus least poor [37.9%]; concentration index 0.131), and 2006 with near-perfect equality (most poor [66.3%] versus least poor [66.6%]; concentration index 0.000). The free mass distribution method achieved highest coverage among the poorest children, the highly subsidised clinic nets programme was marginally in favour of the least poor, and the commercial social marketing favoured the least poor. CONCLUSIONS: Rapid scaling up of ITN coverage among Africa's poorest rural children can be achieved through mass distribution campaigns. These efforts must form an important adjunct to regular, routine access to ITNs through clinics, and each complimentary approach should aim to make this intervention free to clients to ensure equitable access among those least able to afford even the cost of a heavily subsidized net.

In-hospital morbidity and mortality due to severe malarial anemia in western Kenya.

Severe malarial anemia (SMA) is a leading cause of pediatric morbidity, hospitalization, and mortality in sub-Saharan Africa, and yet its contribution to malaria-specific mortality is not well documented. We retrospectively reviewed the clinical records of 1,116 children < 5 years of age admitted to Siaya district hospital, western Kenya, to assess the contribution of SMA to overall in-hospital mortality. Of 1,116 admissions, 86% were under 3 years, 83% had malaria parasitemia, 86% were anemic, 21% were severely anemic, and 20% were transfused. Severe anemia was associated with parasitemia in 85% of the admissions and contributed to 53% of malaria-related deaths. Overall, 83 (7.5%) children died; 66% of those deaths were malaria-related, 12% had severe anemia, and 89% were under 3 years. Transfusion did not lower mortality rates. In areas of high malaria transmission, children below 3 years are a high-risk group for malaria, anemia, blood transfusion, and mortality.