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      Changing malaria intervention coverage, transmission and hospitalization in Kenya

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          Abstract

          Background

          Reports of declining incidence of malaria disease burden across several countries in Africa suggest that the epidemiology of malaria across the continent is in transition. Whether this transition is directly related to the scaling of intervention coverage remains a moot point.

          Methods

          Paediatric admission data from eight Kenyan hospitals and their catchments have been assembled across two three-year time periods: September 2003 to August 2006 (pre-scaled intervention) and September 2006 to August 2009 (post-scaled intervention). Interrupted time series (ITS) models were developed adjusting for variations in rainfall and hospital use by surrounding communities to show changes in malaria hospitalization over the two periods. The temporal changes in factors that might explain changes in disease incidence were examined sequentially for each hospital setting, compared between hospital settings and ranked according to plausible explanatory factors.

          Results

          In six out of eight sites there was a decline in Malaria admission rates with declines between 18% and 69%. At two sites malaria admissions rates increased by 55% and 35%. Results from the ITS models indicate that before scaled intervention in September 2006, there was a significant month-to-month decline in the mean malaria admission rates at four hospitals (trend P < 0.05). At the point of scaled intervention, the estimated mean admission rates for malaria was significantly less at four sites compared to the pre-scaled period baseline. Following scaled intervention there was a significant change in the month-to-month trend in the mean malaria admission rates in some but not all of the sites. Plausibility assessment of possible drivers of change pre- versus post-scaled intervention showed inconsistent patterns however, allowing for the increase in rainfall in the second period, there is a suggestion that starting transmission intensity and the scale of change in ITN coverage might explain some but not all of the variation in effect size. At most sites where declines between observation periods were documented admission rates were changing before free mass ITN distribution and prior to the implementation of ACT across Kenya.

          Conclusion

          This study provides evidence of significant within and between location heterogeneity in temporal trends of malaria disease burden. Plausible drivers for changing disease incidence suggest a complex combination of mechanisms, not easily measured retrospectively.

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          Most cited references34

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          Impact of Artemisinin-Based Combination Therapy and Insecticide-Treated Nets on Malaria Burden in Zanzibar

          Introduction The increased malaria-related morbidity and mortality, especially in children under the age of 5 y (“under five”), due to emerging resistance of Plasmodium falciparum to conventional antimalarial drugs calls for immediate actions to “Roll Back Malaria” in sub-Saharan Africa. This need has been clearly recognized in the Millennium Development Goals “to halt and begin to reverse malaria incidence” [1] as well as in the Abuja Declaration objective to halve malaria mortality in Africa by 2010 through implementation of combined control strategies [2]. In the year 2000, the overall treatment failure of chloroquine was found to be 60% in a 14-d efficacy trial; consequently the Zanzibar Ministry of Health and Social Welfare decided in November 2001 to change both first- and second-line treatment guidelines for uncomplicated malaria from chloroquine and sulfadoxine-pyrimethamine to artemisinin-based combination therapies (ACT) [3]. The ACT policy was implemented in September 2003, when Zanzibar became one of the first regions in sub-Saharan Africa to recommend routine use of ACT. This action was followed by strengthened vector control, culminating in a nation-wide distribution campaign of long-lasting insecticidal nets (LLINs) from early 2006. Both ACT and vector control measures have independently proven to be efficacious malaria control strategies. Ecological studies have credited ACT with enhancing treatment efficacy, reducing malaria transmission, and possibly forestalling drug resistance in low-endemicity areas [4,5]. Moreover, specific African trials have indicated that the use of insecticide-treated nets (ITNs) or indoor residual spraying can reduce mortality of children under five in Africa [6–9]. This is, however, to our knowledge the first study to examine the public health impact of wide-scale deployment of ACTs alone and combined with ITNs through the general health structure/channels on malaria indices and general health parameters in an endemic area in sub-Saharan Africa. Methods Study Site The study was conducted in North A District, Zanzibar, situated just off the coast of mainland Tanzania. The district is rural and has a population of about 85,000. Subsistence farming and fishing are the main occupations. Plasmodium falciparum is the predominant malaria species and Anopheles gambiae complex is considered the main vector. Malaria transmission is stable with seasonal peaks related to rainfall in March–May and October–December. Malaria transmission in the district prior to the interventions has been reported to be high, but specific entomological data are not available to allow a precise characterization of malaria transmission intensity. However, during the screening process of a major antimalarial drug trial conducted in 2002–2003, a P. falciparum prevalence exceeding 30% was observed in febrile children under five [10], suggesting that North A District had been a high transmission area prior to ACT implementation in September 2003. North A District has one Primary Health Care Centre, which includes a hospital with inpatient and laboratory services, e.g., blood transfusion and malaria microscopy services. Basic medical treatment services without laboratory support are provided in 12 Primary Health Care Units located in different shehias (the smallest political administrative unit in Zanzibar). Drugs, including conventional and artemisinin monotherapies, are also available in private shops throughout the district. Malaria Control Interventions Figure 1 illustrates time of implementation of the two malaria control interventions. Figure 1 Malaria Interventions, Cross-Sectional Surveys, Monthly Rainfall, and Reported Clinical Malaria Diagnoses in Children under 5 Years of Age in North A District, Zanzibar (A) Start of the implementation of artemisinin-based combination therapy for treatment of uncomplicated malaria in September 2003. (B) Introduction of LLINs in February 2006. Promotion of ITNs started in January 2004; the use of conventional ITNs, however, remained low, until the introduction of LLINs. Outpatient data for 2006 are up to June. First intervention—ACT. A loose combination of artesunate and amodiaquine (AS+AQ; from various suppliers with preapproval from WHO) and a fixed combination of artemether–lumefantrine (Coartem; Novartis, Basel, Switzerland), were implemented as first- and second-line treatment, respectively, for uncomplicated malaria in all public health facilities from September 2003. In a pre-implementation assessment of the new treatment policy, partly conducted in North A District 2002–2003, both AS+AQ and artemether–lumefantrine were highly efficacious with PCR-adjusted cure rates by day 28 above 90% [10]. Quinine remained the drug of choice for severe malaria and sulfadoxine-pyrimethamine for intermittent preventive treatment during pregnancy. From September 2003, chloroquine was withdrawn from all health facilities and replaced by free provision of ACT to all malaria patients. Total treatment courses of AS+AQ dispensed in North A 2004 and 2005 were 34,724 and 12,819, respectively. The supply of ACT has been uninterrupted, with no reports of AS+AQ being out of stock from any public health facility in the district during 2003–2006 (unpublished data). ACTs were purchased with support from African Development Bank and Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM). Second intervention—vector control. A policy to distribute conventional ITNs to the most vulnerable groups—children under five and pregnant women—free of charge through antenatal clinics or local shehia leaders was officially launched in 2004. However, ITN coverage and use remained low in North A District 2004 and 2005 due to limited number of ITNs distributed, 4,026 and 1,550, respectively. A mass campaign was therefore initiated early 2006, with distribution of 23,000 LLINs to the two most vulnerable groups in North A. This campaign was supported by GFATM and the US Agency for International Development. Cross-Sectional Surveys Three cross-sectional surveys with the primary objective to determine P. falciparum prevalences were conducted in North A District between 2003 and 2006. A two-stage cluster sample technique was used. First shehias and then the households were randomly selected from the sampling frame obtained from the Office of Chief Government Statistician, Zanzibar. The sampling frame was updated before each survey. The first exploratory survey, conducted in May 2003, included 625 households and provided baseline data prior to ACT and widespread ITN implementation. Sample size calculations for the follow-up surveys conducted in May 2005 and 2006 were based on the proportion of children under five with malaria parasitemia in 2003, about 9%, and an assumed relative error of 20%. The calculated number of households to be included was 490 after adjusting for a design effect of 2. Trained interviewers visited all selected households. Interviews and blood sample collection were initiated upon written consent from head of each household and proxy consent from the mother or guardian of each child. Information was recorded using a structured questionnaire on recent febrile illness, mosquito net use, and care-seeking behavior from each individual present in the household at the time of the survey. We did not replace households in which residents were not present at time of survey, could not be located, or refused to participate. Thick blood films were collected from all consenting participants, stained with 5% Giemsa for 30 min, and examined by experienced microscopists for presence and density of P. falciparum parasites. If fewer than ten parasites were detected per 200 white blood cells, examinations were extended to 500 white blood cells. Blood slides were considered negative if no asexual parasites were found in 200 high-power fields. High-density parasitemia was defined as presence of ≥ 5,000 parasites/μl [11]. Quality control was conducted for all positive slides and 10% of the negative slides [12]. Health Facility Records Malaria-related indicators, i.e., outpatient attendances, hospital admissions and blood transfusions, from all 13 public health facilities in North A District were obtained from the Health Management and Information System (HMIS) records of the Zanzibar Ministry of Health and Social Welfare. The existing HMIS records were about 90% complete for the period 2000–2004. Data were validated and missing information retrieved by retrospective review of source documents from all 13 health facilities. This confirmed the HMIS records and resolved missing or inconsistent data, which increased the completeness to nearly 100%. A database of malaria-related indicators was created on the basis of this retrospective review. Data from 2005 were abstracted on quarterly basis. Vital Statistics Records of vital events, i.e., births and deaths, for the period 1998–2005 were obtained from the District Commissioner's Office (DCO) in North A. Annual crude mortalities of children under five were estimated from these data. Demographic estimates were obtained from Tanzania National Population and Housing Census 2002. Rainfall Complete records of monthly rainfall during 1999–2005 were obtained from official registers of the Tanzania Metrological Agency of the Ministry of Communications and Transport. On Unguja island, rainfall is centrally measured in one weather station, situated 26 km (radially) from North A District. The mean annual rainfalls recorded in 2003, 2004, 2005, and 2006 were 702, 1,934, 1,231, and 1,214 mm, respectively. The corresponding mean seasonal rainfall (March–May) between 2003 and 2006 was 285, 786, 890, and 613 mm, respectively. During the post-ACT intervention period (2004–2006) the mean annual and seasonal rainfall was 8%–12% lower than the pre-ACT intervention period (2000–2002). However, the only year with a marked reduction in the mean annual and seasonal rainfalls was the year 2003 with two- to three-fold lower rainfall, as compared to both the preceding and subsequent 3 y. Data Processing and Analysis Data were entered and validated using Microsoft Access and Excel. Statistical analyses for cross-sectional surveys, health facility records, vital statistics, and rainfall data were performed using Stata version 8. Analysis for the surveys was corrected for multi-stage sampling errors using the Rao-Scott second order correction [13]. A logistic regression model with robust standard errors (robust cluster) was used to adjust for the effect of age, sex, sleeping under a mosquito-net, and asset index on asexual P. falciparum prevalence and gametocyte carriage across the study years. Households were the primary sampling units in the surveys and were defined as clusters. Wald test was used to assess the fit of the model and interactions between covariates incorporated in the model. Odds ratios were adjusted for the complex sampling design and covariates listed above. Pearson correlation coefficients were calculated to assess the linear relationships between monthly rainfall and outpatient malaria diagnosis, and malaria-attributed deaths. Ethical Approval Protocols for the household surveys were reviewed and approved by the Medical Research Coordinating Committee of the Tanzanian Commission on Science and Technology, the Zanzibar Health Research Council and the institutional review board of US Centers for Disease Control and Prevention. Results Cross-Sectional Surveys The timings of the cross-sectional surveys in relation to start of each malaria control intervention and seasonal rainfalls are presented in Figure 1. The number of households enrolled and participant characteristics in the respective surveys are shown in Table 1. Over 95% of all participants agreed to both answer questionnaires and provide blood samples in the respective surveys. Table 1 Number of Households Surveyed and Characteristics of Survey Participants The parasite prevalences and odds ratios (ORs) of asexual P. falciparum parasitemia and gametocyte carriage at the time of cross-sectional surveys are shown in Table 2. Between 2003 and 2005 the parasite prevalence was reduced by about 50% in children under five. A further 10-fold decrease in P. falciparum prevalence was observed between 2005 and 2006, following mass distribution of LLINs specifically targeting this age group. Concomitant reductions of parasite prevalence were observed in children over the age of 5 y, although only by about 3-fold, between 2005 and 2006 (OR 0.41, 95% confidence interval [CI] 0.13–1.21), p = 0.08). Table 2 Parasite Prevalence and ORs of P. falciparum Asexual Parasitemia and Gametocytemia in Children 0–14 Years of Age in North A District, Zanzibar, in May 2003, 2005, and 2006 High-density parasitemia (≥5,000/μl) was found in 14 (2.7%) and 2 (0.6%) children under five in 2003 and 2005, respectively. No child carried high-density parasitemia in 2006. Reported fever within 14 d prior to the survey was similar in 2003 and 2006 among children under five (2003, 13% [95% CI 11–17]; 2006, 12% [95% CI 9–16]), whereas care-seeking at public health facilities by recently febrile children under five increased significantly (2003 was reference year; 2005, OR 3.91 [95% CI 0.85–17.9]; 2006, OR 5.5 [95% CI 2.3–13.3]; p-value for trend < 0.001). The proportions of children under five sleeping under effective ITNs were below 10% in both 2003 and 2005 (Table 1), whereas in 2006, 90% were reported sleeping under an LLIN on the night before survey. Health Facility Surveillance All reported clinical outpatient malaria diagnoses in North A District between January 1999 and June 2006 among children under five are shown by month in Figure 1 and by year in Table 3. Between 2002 and 2005 the total number of out-patient malaria diagnoses decreased by 77%. The annual incidences of malaria diagnoses standardized per 1,000 children under five in North A District were 843, 786, and 233 in 2003, 2004, and 2005, respectively. The total number of children under five attending public health facilities for any cause during 1999 and 2005 remained relatively constant, ranging from 31,069 to 39,374 annually. Up to 2003 malaria accounted for about 50% of all outpatient diagnoses in this age group, whereas in 2005 this proportion had decreased to 13%. Table 3 Outpatient Malaria Diagnoses, Hospital Admissions, Blood Transfusions, and Malaria-Attributed Deaths in North A District, Zanzibar, between 2000 and 2005 Malaria-related hospital admissions, non-malaria admissions, and blood transfusions in children under five between 2000 and 2005 are also shown in Table 3. From 2002 to 2005, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased by 77%, 67%, and 75%, respectively. Crude Mortality Data A total of 23,200 live births and 1,032 deaths in children under five (49% females) were registered between January 1998 and December 2005. The annual mortality figures for children under five, children (1–4 y), and infants (0–1 y) are shown in Table 4. Between 2002 and 2005, crude under five, infant, and child mortality decreased by 52%, 33%, and 71%, respectively. Table 4 Mortality of Children under 5 Years of Age in North A District, Zanzibar between 1998 and 2005 Relationships between Rainfall and Malaria Diagnosis and Deaths In the pre-ACT intervention period (2000–2002), significant positive correlations were found between monthly rainfall and both outpatient malaria diagnoses (Pearson correlation coefficient [r p] = 0.59, p < 0.001) and malaria-attributed deaths (r p = 0.75, p < 0.001), when data were adjusted to allow for a 1-mo lag between rainfall and malaria diagnoses and deaths. However, in the post-ACT intervention period (2003–2005), no significant correlations were found between monthly rainfall and outpatient malaria diagnosis (r p = −0.05; p = 0.75) or malaria-attributed deaths (rp = 0.23; p = 0.20). Discussion Malaria burden in Zanzibar, as in most parts of sub-Saharan Africa, has remained high and in many areas even increased during the last 10–20 y, a major reason being rapid spread of resistance to commonly used monotherapies against malaria. This problem has necessitated urgent implementation of new and effective control strategies to “Roll Back Malaria.” Two main cornerstones in this effort are the introduction of ACTs for treatment of uncomplicated malaria and the promotion of ITN use. The targets for the implementation of these new strategies have been defined by the UN Millennium Development Goals [1] and the Abuja Declaration [2], to be achieved by the years 2015 and 2010, respectively. Deployment of ACTs The ACTs were dispensed free of charge to all patients in the study area through public health facilities from September 2003 onwards. The ACT implementation and deployment was very rapid, effective, and with high coverage. Monitoring of drug supplies confirmed that ACTs were available throughout the study period in all 13 public health care settings in North A District. This outcome also indicates that estimates were adequate of the needed and thus deployed numbers of ACT treatments in the district. This result was accomplished despite an apparent two-fold increase in care seeking among children under the age of 5 y at public health facilities as observed in the cross-sectional surveys. We believe that the observed shift in treatment-seeking behavior at public facilities may be related to availability of free, effective ACTs. A previous study in Zanzibar showed that people's attitudes towards health seeking at public health facilities (biomedical practices) are negatively influenced by the distribution of ineffective antimalarial drugs [14]. High ACT coverage was rapidly achieved in malaria patients despite availability of other drugs in the private sector. This achievement was probably influenced both by comprehensive information to the public and health care staff and by the strong commitment of the Zanzibar government to rapidly ensure free coverage of the ACTs. Also, in North A District, as well as in Zanzibar generally, the entire population has relatively easy access to public health facilities, which are located within 5 km from any community and are served by good transport links. However, the absence of co-formulation or even of co-blistering of the two compounds in the first-line treatment, artesunate and amodiaquine, may have resulted in some degree of monotherapy with either compound. Mortality Impact Our study provides the first, to our knowledge, observation of a reduction in mortality of children under five following introduction of ACTs solely in a stable malaria-endemic setting. The highly significant reduction of 52% in crude under-five mortality according to vital statistics between 2002 and 2005 also highlights the importance of malaria as a major cause of death among children in malaria-endemic areas. The 71% reduction among children aged 1–4 y indicates that the relative contribution of malaria to crude mortality is particularly important in this age group. Major reductions in crude under-five mortality has also been observed in previous randomized intervention studies with ITNs [6,7] and community-based malaria treatment [15,16], but the reduction rates (between 25% and 40%) have been less pronounced than those in our study in Zanzibar. We believe our findings are valid and represent a true picture of the effects of ACT deployment in North A District, Zanzibar. No other major political, socioeconomic, or health-care change with the potential to halve mortality in children under five occurred in Zanzibar after 2002. This includes Expanded Programme on Immunization coverage, which remained constantly above 80% in the district during 1999–2005. Furthermore, there was no significant change in rainfall that may have contributed to the observed reduction in malaria transmission. Indeed, the only year with reduced rainfall with potential influence on vector capacity occurred before the introduction of ACTs—in 2003. Increased use of ITNs may also represent a potential confounding factor in our study. However, the ITN use was below 10% during 2004 and 2005 as reported and observed during the cross-sectional surveys. A significant improvement in ITN coverage was only achieved in 2006 after the introduction of LLINs (see further below) and only affected the 2006 cross-sectional results. We chose 2002 as reference year in our analyses of health facility surveillance and under-five mortality, because 2002 represents the last complete year before ACT introduction in September 2003. Routinely collected mortality statistics may underestimate the true values. However, such data have been shown to provide valid mortality trends [17,18]. Morbidity Impact A significant reduction was found with regard to hospitalization of malaria patients and incidence of blood transfusions, which may be considered proxy indicators of severe malaria. The reduction of severe malaria showing a similar pattern thus supports the under-five mortality trends. This health impact probably represents effects of improved case management of uncomplicated malaria with ACT, thus preventing the development of severe manifestations of the disease. The decrease in malaria morbidity (and mortality) at health facilities between 2003 and 2005 confirms the therapeutic efficacy of ACT [10], but the reduction in outpatient malaria diagnoses may also reflect some transmission blocking effect of artemisinin derivatives through its gametocytocidal activity. Reduction in transmission potential has been suggested after the introduction of artemisinin derivatives (before vector control) for routine treatment in a low and seasonal malaria transmission setting in Thailand [4]. Data obtained from routine health facility records have inherent potential pitfalls and need to be interpreted cautiously. However, the fact that they all show the same downward trend after improved coverage of malaria prevention and treatment interventions, and with no change in the climatic conditions that are favorable for malaria transmission, supports the plausible conclusion that enhanced malaria control interventions contributed to the observed public health benefits. Deployment of ITNs The deployment of LLINs in early 2006 provided a high coverage, i.e., over 90% reported use in children under five in the cross-sectional survey in May 2006. Importantly, this high mosquito-net use was observed after strong government commitment and after free LLIN distribution to children under five and pregnant women. The most significant decrease in prevalence of asymptomatic parasitemia was achieved in 2006, when LLINs were widely used by the children under five, whereas the major impact on the under-five mortality was achieved earlier with ACT use only. Strengthened vector control and the use of ACT also resulted in marked and sustained malaria control in South Africa [5]. The similar public health benefits observed in North A supports the concomitant use of vector control and ACT for malaria control. However, it should be emphasized that our study captures short-term trends in malaria control in North A, which may be too short to generalize long-term trends in the burden of malaria. Sustained coverage and use of LLINs by vulnerable groups is yet to be demonstrated, especially under declining malaria endemicity and if the free LLIN distribution scheme were to be changed. Conclusions The declining under-five mortality, malaria morbidity, and malaria prevalence observed in our study is the first comprehensive evidence supporting the major public health benefits of ACT and ITNs in a stable endemic malaria transmission setting in sub-Saharan Africa. The findings suggest that ACTs with high coverage of ITN use may potentially even eliminate malaria as a public health problem in highly endemic areas of sub-Saharan Africa. High community uptake of the two interventions is probably required but indeed achievable if, as in our study, they are easily available free of charge. The UN Millennium Development Goals to alleviate malaria as a major public health problem and substantially reduce the under-five mortality in sub-Saharan Africa are thus achievable even in settings with historically intense malaria transmission. The sustainability of these efforts as well as surveillance to prevent resurgence of malaria represent key research and programmatic follow-up issues of malaria control in Africa.
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            Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya

            Summary Background As efforts to control malaria are expanded across the world, understanding the role of transmission intensity in determining the burden of clinical malaria is crucial to the prediction and measurement of the effectiveness of interventions to reduce transmission. Furthermore, studies comparing several endemic sites led to speculation that as transmission decreases morbidity and mortality caused by severe malaria might increase. We aimed to assess the epidemiological characteristics of malaria in Kilifi, Kenya, during a period of decreasing transmission intensity. Methods We analyse 18 years (1990–2007) of surveillance data from a paediatric ward in a malaria-endemic region of Kenya. The hospital has a catchment area of 250 000 people. Clinical data and blood-film results for more than 61 000 admissions are reported. Findings Hospital admissions for malaria decreased from 18·43 per 1000 children in 2003 to 3·42 in 2007. Over 18 years of surveillance, the incidence of cerebral malaria initially increased; however, malaria mortality decreased overall because of a decrease in incidence of severe malarial anaemia since 1997 (4·75 to 0·37 per 1000 children) and improved survival among children admitted with non-severe malaria. Parasite prevalence, the mean age of children admitted with malaria, and the proportion of children with cerebral malaria began to change 10 years before hospitalisation for malaria started to fall. Interpretation Sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies. Changes in transmission might not lead to immediate reductions in incidence of clinical disease. However, longitudinal data do not indicate that reductions in transmission intensity lead to transient increases in morbidity and mortality. Funding Wellcome Trust, Kenya Medical Research Institute.
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              Increasing Coverage and Decreasing Inequity in Insecticide-Treated Bed Net Use among Rural Kenyan Children

              Introduction The gulf between levels of childhood mortality in sub-Saharan Africa and access to simple, cost-effective interventions known to significantly reduce mortality is immoral [1]. For over ten years it has been known that insecticide-treated bed nets (ITNs) can reduce childhood mortality by 17% [2]. In 1998 the Roll Back Malaria (RBM) movement was launched with one of its primary objectives to increase ITN coverage among vulnerable groups, such as children and pregnant women, to over 60% [3]. RBM has recently revised this ITN objective to reach 80% coverage by 2010 [4]. This change in target followed the RBM publication of the current status of ITN coverage in Africa as part of its World Malaria Report [5]. Of 34 malaria-endemic countries in Africa providing recent national data, only one (Eritrea) had achieved ITN coverage among children aged less than 5 y of more than 60% [5]. Reasons for this dismal progress has been the subject of much debate [6–9] and largely centre around divergent views on optimal strategies to deliver ITNs to economically and biologically vulnerable groups across Africa. During the early days of RBM, the technical advice to countries provided by World Health Organization (WHO) was to create an “enabling environment” that allowed malaria-endemic countries to embrace multiple approaches to providing ITNs [10]. These approaches included building sustainable private for-profit markets, for example through the NETMARK initiative in nine African countries [11]; creating a not-for-profit commercial sector through social marketing, a model promoted by Population Services International (PSI) operating in 23 African countries [12]; or the less popular at the time option of providing ITNs free of charge through clinics, or as first suggested in 1995, through vaccine campaigns [13]. The best-practice debate has been driven by personal opinion [6,7] or data on temporal changes in ITN coverage associated with single delivery approaches [14–16]. Where data exist they compare information on a single delivery model against a baseline without significant intervention or iterative increases in net coverage associated with a single, nationally adopted approach to delivery. Rarely is it possible to compare incremental coverage associated with different delivery models. Here we present a serial observation of ITN coverage among rural Kenyan communities exposed at different times to the range of delivery models each with legitimate claims to improve ITN access. Our emphasis throughout this study was to examine how ITN access by the poorest sectors of rural communities might best be achieved with each approach. Methods The Kenya ITN Context Prior to the launch of Kenya's National Malaria Strategy in April 2001 [17], access to nets was limited to the private for-profit retail sector and special project-based distributions through research- or nongovernmental organization-led community development initiatives [18]. In 2000 the Kenya Ministry of Health (MoH) developed with partners an ITN strategy paper [19] that attempted to accommodate two competing views on ways to reach the government's target of 60% coverage of populations at risk by 2005. The first approach included ways to ensure that the ITN market is self-sustaining in the absence of long-term donor support by expanding the private sector through social marketing; the second approach, principally favoured by the MoH, was to provide ITNs free of charge to pregnant women and children under the age of 5 y to achieve rapid scale-up. In January 2002 the UK Department for International Development (DFID) awarded PSI-Kenya US$33 million over 5 y to socially market partially subsidised ITN within the existing retail sector. The programme, named PSI Coverage Plus, was the only major operational ITN distribution initiative between 2002 and 2004 and aimed to target urban and rural retail outlets with Supanet ITNs across all malaria-endemic districts in Kenya. A two-tier pricing system of 350 Kenya Shillings (KES) (equivalent to US$4.7) in urban settings versus KES100 (US$1.3) in rural settings was implemented. The programme's aims were to increase community awareness of the value of ITNs thus creating a “net culture”; force existing retail prices down; and increase clients' willingness to pay for nets through a sustainable, unsubsidised commercial market [20]. In June 2004, DFID approved an additional US$19 million to PSI to establish a parallel distribution system of heavily subsidised ITNs to children and pregnant women through Maternal and Child Health (MCH) clinics, recognizing that these vulnerable groups might not be able to access socially marketed commercial sector nets. The programme began in October 2004, and during the first 6 mo Supanet ITNs were bundled with separate Powertab net treatment tablets (for every 6 mo) and distributed to MCH attendees. In May 2005 an additional US$37 million was committed by DFID to PSI to procure and distribute Supanet-branded long-lasting insecticidal nets (LLINs), Olyset and Permanet. These public sector nets were heavily subsidized pretreated nets (KES50; US$0.7) and branded with the MoH logo [20]. In February 2002 the MoH responded to the first call of the Global Fund to Fight AIDS, TB and Malaria (GFATM) for funding applications to secure five million nets and net treatments to provide free of charge to children under the age of 5 y and pregnant women. This application was unsuccessful. During round four of the GFATM awards in April 2004, Kenya's application was successful and US$17 million was approved to procure and distribute 3.4 million LLINs (Olyset and Permanet brands) free of charge to children under the age of 5 y. This represented, at the time, the largest successful award for free distribution of LLINs in Africa. The implementation of the free mass distribution of LLINs was arranged in two phases during 2006. During the first phase, 21 of Kenya's 70 districts were selected for distribution of LLINs from 8 to 12 July 2006 and integrated with the national measles catch-up vaccination campaign. Health facilities and centralised non-health facility posts were identified by the Kenya Expanded Programme on Immunisation and used as delivery points of both measles vaccine and LLINs to each child under the age of 5 y. A second mass distribution of LLINs, not integrated with any other intervention, took place from 25 to 27 September 2006 in 24 additional districts using previous mass vaccine campaign delivery centres as distribution points. Study Area The study was carried out in four districts purposively sampled in collaboration with the MoH to provide detailed longitudinal milestone data on changing access to interventions proposed within the Kenya National Malaria Strategy between 2001 and 2006 [21,22]. The study districts represent the range of dominant malaria epidemiological situations that prevail across Kenya: Kwale on the coast with seasonal high-intensity malaria transmission; Bondo on the shores of Lake Victoria with perennial high-intensity transmission; Greater Kisii district (combining the new districts of Kisii Central and Gucha) with seasonal low transmission conditions of the Western highlands; and Makueni district, a semi-arid area with acutely seasonal low malaria transmission. Between 63% and 71% of households in the rural areas of each of the four districts were living below the poverty line (equivalent to US$1 per day) in 1999, compared to the national average of 54% [23]. The districts were also representative of rural districts in Kenya with respect to net delivery since 2001, with service providers including the full-cost commercial and social marketing retail sector; a research team in parts of Bondo district [24]; nongovernmental organization delivery to selected communities in Greater Kisii (Merlin and World Vision) and Kwale (Plan International and The Aga Khan Foundation); time-limited MoH provision of free nets to pregnant women in 2001 in all districts [25] and to children and pregnant women in Bondo and Gucha districts in 2005 [26]; and subsidized PSI clinic distribution since October 2004 and mass, free distribution in 2006 across all districts. Within each district, rural enumeration area (EA) boundaries were digitized with ARCGIS 9.0 (ESRI, http://www.esri.com/) and each polygon attributed to population totals derived from the last national census in 1999 [27]. A sample of 18 rural EA polygons, covering approximately 6,500 people per district, was randomly selected from each district to form the basis of the longitudinal community surveillance. Following community sensitisation, all homesteads within an EA polygon were mapped and heads of homesteads were given the purpose of the longitudinal study and asked whether they wished to participate. All de jure resident homestead members were enumerated, including details of date of birth and sex, and issued a unique identifier for follow-up. The Longitudinal Cohort During December/January of 2004/5, 2005/6, and 2006/7, just after the short rains, a cohort of children under the age of 5 y was established to track, by interviewing mothers or caretakers, the ownership and use of bed nets, including details on the net brand, where and when they were obtained, and whether nets had been treated with an insecticide during the previous 6 mo. Interviewers were instructed to observe the nets and record details of the colour, imprinted logos, and shape of the net to match the net types delivered by different partners in each district at different times. All children resident in 2004 were recruited into the cohort and exited during subsequent census rounds if they had out-migrated, homesteads or guardians subsequently refused participation, they had reached their fifth birthday, or they had died. New children were recruited into the cohort if they had migrated into the homestead between census rounds or were identified through detailed birth histories of all resident women aged 15–49 y as having been born during the interval. New infants who did not survive the interval between census rounds were included in the cohort. In-migrations that out-migrated between the census rounds were not included in the cohort and were regarded as short-term visitors not permanently resident. During the 2005/6 annual census round, representing the reference midpoint of the surveillance period, details were recorded on each homestead relating to key asset indicators, including: homestead head education level and occupation; housing characteristics (type of wall, roof, and floor); source of drinking water; type of sanitation facility; homestead size; and persons per sleeping room (see Table S1). Data Entry and Analysis Data entry and storage were undertaken using Microsoft Access, and analysis was undertaken using STATA version 9.2 (Stata, http://www.stata.com) and ARCGIS 9.0 (ESRI). All information specific to the EA, homestead, and mother or guardian were linked to the relevant child through the use of a primary homestead identifier consistent across all data sets. To account for unequal probabilities of selection of EAs, all results were weighted (weight = 1/probability of selection) and precision of proportions (95% confidence intervals [CIs]) were adjusted for clustering with EA as the primary sampling unit. A χ2 test was performed to compare net use proportions across subgroups within and between survey years. For comparisons of socioeconomic groups within a survey year, the Pearson χ2 statistic, accounting for clustering, was used. This statistic is turned into an F-statistic using the second-order Rao and Scott correction and p-values interpreted the same way as the Pearson χ2 statistic for data without clustering [28,29]. A homestead wealth index was constructed from the asset indicators using principal component analysis. Weights (scoring coefficients) derived from the first principal component were used to construct the wealth index [30]. Weights for each asset indicator from the first principal component were then applied to each homestead record to produce a wealth index. Wealth asset indices were developed separately for each district to allow for innate differences in the meaning of different assets between districts. Each homestead was then assigned to a district-specific wealth quintile. Net ownership by children in the cohort was examined serially and by source according to wealth asset quintiles. Inequity in net coverage over time and by source was analysed using the concentration index, which gives values between −1 and 1, with a value 0 indicating an absence of wealth-related inequality in net use among children [31]. Because net use is a “good” health variable, a positive value of the index indicates net use is concentrated among the wealthy. The concentration curve was plotted to illustrate changes in wealth-related inequality [31]. Ethical Approval Ethical approval was provided by the National Ethical Review Board IRB (Kenya Medical Research Institute SSC number 906). Results A total of 2,761 homesteads were selected across the 72 rural communities located in the four districts in 2004. Three homesteads refused participation in 2004 (0.01%); 11,050 observations of children under the age of 5 y were made across the three survey years in 2004/5, 2005/6, and 2006/7. Over the three years, 155 (1.4%) usually resident children were visiting elsewhere at the time of the annual surveys, 66 (0.6%) children's parents or guardians refused to be interviewed and 133 (1.2%) children died before the census rounds in 2005/6 and 2006/7. In 2004/5 the weighted proportion of children usually using a net, adjusted for clustering, was 13.9%, similar to the proportions of children using a net the night before the survey (Table 1). The small difference between usual use of a net and net use the night before survey was a consistent finding across all surveys (Table 1). We elected to restrict subsequent analysis to net use the night before survey. In 2004/5 the majority of children (65%) who slept under a net were sleeping under nets purchased from the commercial retail sector, only 7% of children slept the night before the survey under nets treated with an insecticide within the last 6 mo, and the proportion ITN use among children living in the poorest quintile homesteads was one-fifth (2.9%) to the proportion of those living in the least poor homesteads (Table 1). Table 1 Net Usage by Children across Four Districts in Three Consecutive Survey Years In December/January 2005/6, 12 mo after the baseline survey, the proportions of children sleeping under a net had increased to 32% where the dominant net source was the heavily subsidized PSI-MCH clinic nets; 58% of children using a net were using nets from this source (Table 1). The proportion of children sleeping under a net treated with an insecticide in the last 6 mo had tripled to over 23% compared to 2004/5 (p < 0.001). Children living in the poorest homesteads had proportionately the largest (six-fold) increase in ITN use over the 12 mo interval, rising from 2.9% in 2004/5 to 17.5% in 2005/6 (p < 0.001); however, children living in the least poor homesteads were still twice as likely to have slept under an ITN the previous night as those in the poorest homesteads (Table 1). These results are reinforced by the concentration indices, which remained positive (net use highest among the wealthier groups) in both rounds of the survey, although the measure of wealth-related inequality, the concentration index, fell from 0.281 in 2004/5 to 0.131 in 2005/6. By December/January 2006/7, the proportion of children sleeping under a net increased to 81%, with the two dominant sources of nets being the free mass campaign (44%) and the PSI-MCH clinics (41%) (Table 1). Within 12 mo of the previous survey, the proportion of children sleeping under an ITN had doubled to 67%; 44% of children were sleeping under an ITN provided during the mass campaign. The largest increase in the proportion of children sleeping under an ITN was among those from homesteads in the poorest quintile, from 17.5% in 2005/6 to 66.3% in 2006/7. There was no statistically significant difference in the proportion of children using an ITN between highest and lowest wealth quintiles in 2006/7 (p = 0.963). The poverty concentration index declined from 0.131 in 2005/6 to 0.000 in 2006/7 (Table 1). The concentration curve indicated, for the first time, the absence of wealth-related inequality in net use (Figure 1) further illustrated by the graph of actual proportions (Figure 2). Figure 1 Degree of Inequality in Children Sleeping under an ITN in 2004/5, 2005/6, and 2006/7 in Homesteads of Different Wealth Status in the Four Districts in Kenya The concentration curve below the line of perfect equality indicates that ITN use is concentrated among higher socioeconomic groups. When the curve is coincident on the line of perfect equality, then there is no wealth-related inequality in ITN use. Figure 2 Proportion of Children Sleeping under an ITN in 2004/5, 2005/6, and 2006/7 in Homesteads of Different Wealth Status in Four Districts in Kenya By the end of September 2006, the three principal net distribution strategies (retail social marketing, heavily subsidized clinic distribution, and free mass distribution) were all operating in parallel, providing an opportunity to examine socioeconomic targeting of each of the delivery mechanisms (Table 2). In 2006/7 2.4% and 24.3% of children from the poorest homesteads slept under a net from the retail sector and the PSI-MCH programme, respectively, compared to 6.4% and 30.8% from the least poor. Conversely, by 2006/7 the highest proportion of children from the poorest homesteads slept under nets from the free mass campaign (most poor/least poor: 36.6%/25.8%). This pattern is further illustrated by the concentration curve (Figure 3), which shows that the free mass campaign is the only delivery channel favouring the poorest children; the PSI-MCH programme was marginally in favour of the least poor, and the commercial sector was the most inequitable in favour of the least poor. Table 2 Variations in Children's Net Use the Night before the 2006/7 Survey by Source across Different Socioeconomic Groups Figure 3 Degree of Inequality in Socioeconomic Targeting by the Three Principal Net Delivery Mechanisms in Four Districts in Kenya by 2006/7 Delivery mechanisms included commercial social marketing, the PSI-MCH programme, and a free mass campaign. Discussion We have shown that a concerted, multi-pronged approach to ITN delivery in rural areas of Kenya over 3 y resulted in over 60% of children sleeping under a net treated with insecticide, surpassing the original RBM target set in Abuja in 2000 [3]. However, at the end of 2004 this target seemed almost unattainable, with only 7% of rural children reported to be sleeping under an ITN and only 3% among the poorest sectors of these communities. Radical changes in bilateral support to PSI to adapt their social marketing strategy to included MCH clinics resulted in important changes in ITN coverage (24%) by the end of 2005, but coverage still favoured the least poor children. The most dramatic increases in ITN coverage were seen during the last year of the surveillance period at the end of 2006. Through two single mass campaigns in July and September 2006, coverage of ITN use rose to over 67% and was particularly successful at reaching the poorest children (Tables 1 and 2). The concentration index of ITN coverage, which is a measure of inequality, decreased from 0.281 in 2004/5 to 0.000 in 2006/7, indicating an absence of inequality in net use (Figures 1 and 2; Table 1) coincidental with the expansion in different mechanisms of delivery. In recent years, there has been a consensus among national ministries of health, development partners, and other stakeholders that access to health interventions should be made pro-poor [30]. Although gaps in ITN coverage between the least- and most-poor groups have been declining elsewhere in Africa [5], the most-poor remain the least well covered. Our results show that ITN coverage among children was similar across all wealth groups by 2006/7. and nets provided through the free mass campaign actually preferentially covered children from the poorest-quintile homesteads while the heavily subsidised PSI-MCH clinic nets was considerably more equitable than the commercial social marketing (Figure 3; Table 2). Elsewhere in Africa pro-poor ITN interventions have been reported [32–35], but these efforts have been relatively small in scale. To the best of our knowledge this is the first time in Africa that a large-scale public health intervention, covering millions of people, has preferentially reached the most-poor quintiles of a community when compared to the least poor. Unlike single cross-sectional surveys of ITN coverage, the value of the present study is its longitudinal observations among the same homesteads exposed at different times to different systems of delivery. Such data help inform debates on whether ITN delivery should be free or subsidized and whether they should be provided through routine clinics, mass campaigns, or the private sector. Our data clearly show that the most effective means to rapidly scale up ITN coverage, particularly among the poor, is through targeted free distributions, preferably coincidental with other campaigns such as mass vaccination. However, it does not necessarily follow that this should represent the only mechanism by which treated nets are distributed to rural communities. The PSI programme of heavily subsidized net delivery through over 3,000 clinics since October 2004 has reported over 5 million sales of nets [20]. The complex distribution, ordering, and logistics of net commodities were run efficiently by an externally funded and managed system with the infrastructure and staff provided by the government and mission sectors [36]. Although there are no data to support the claim that the provision of subsidized nets at clinics increased use of health facilities, this may have occurred and is a similar argument used to increase attendance at mass Expanded Programme for Immunisation vaccine campaigns that provide free nets [15]. The PSI programme, however, did not reach nationally or internationally agreed targets of ITN coverage within the specified timelines. Similarly routine Expanded Programme for Immunisation services, provided free at clinics, often fail to reach their anticipated coverage targets [37]. We would argue that the constant availability of ITNs at clinics provides an essential early entry point for net use, particularly among young pregnant women who would otherwise not have access to ITNs if restricted to a single annual event targeting children as part of a mass distribution campaign. For vaccine-based programmes to retain effective herd immunity, periodic catch-up campaigns of single mass coverage of vulnerable populations are necessary. We would view this as an analogous position for effective ITN coverage. It is therefore not a question of choosing between the strategies but how to effectively combine them. Some sectors of our rural communities can afford subsidized ITNs, but when only these nets are available the most-poor access them least. It is likely that those bearing the brunt of the malaria burden in rural areas are those most distal to health services and the poorest. Provision of free nets would benefit these communities most. Our results are far less supportive of international donor-promoted efforts to expand the commercialization of ITN distribution in Africa [8,11]. This approach clearly failed to reach those most in need in Kenya, and despite aggressive marketing campaigns, and development of branded products and branded outlets, the incremental gains in ITN coverage were minimal. To effectively integrate routine versus mass campaign ITN distribution requires careful planning. It is important that when planning integrated free mass campaigns, each component of the package is not jeopardized by the other, for example delaying immunization to meet the needs of ITN distribution. In Kenya, funding for the donor-supported PSI programme ends in 2007. Funds are available from the GFATM and the World Bank Booster Programme during 2007 and 2008 to continue LLIN distribution through mass campaigns. Replacing or “permanently” treating existing non-LLINs, covering future vulnerable pregnant women and their infants and expanding to pockets of the country where coverage has remained low all require long-term sustainable financing planned against projected spatially defined needs. These combined approaches require long-term evaluations, modelled on the approach presented, to monitor the synergies between delivery strategies to make sure they retain the equity required to reach those most in need. Whether funding for combined models of delivery comes from national budgets, direct budgetary support from donors, or through mechanisms such as the GFATM, Presidents Malaria Initiative, or the World Bank is beyond the scope of this paper. What we can say is that if funding is not secured for clinic supply and catch-up mass campaigns for LLIN delivery beyond 2008 the impressive, rapid progress toward the RBM target of 80% coverage by 2010 in Kenya will be lost. Supporting Information Table S1 Asset Indicators and Their Weights Computed Using Principal Component Analysis to Construct Homestead Wealth Quintile Rankings for Each District (45 KB DOC) Click here for additional data file.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2010
                15 October 2010
                : 9
                : 285
                Affiliations
                [1 ]Malaria Public Health & Epidemiology Group, Centre for Geographic Medicine Research - Coast, Kenya Medical Research Institute/Wellcome Trust Research Programme, P.O. Box 43640, 00100 GPO, Nairobi, Kenya
                [2 ]Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, CCVTM, Oxford OX3 7LJ, UK
                Article
                1475-2875-9-285
                10.1186/1475-2875-9-285
                2972305
                20946689
                d0553c50-aab4-4c1d-9220-53c646018a51
                Copyright ©2010 Okiro et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 July 2010
                : 15 October 2010
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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