Case Report: Primaquine Failure for Radical Cure of Plasmodium vivax Malaria in Gambella, Ethiopia.

Failures of primaquine for the treatment of relapsed Plasmodium vivax malaria is a serious challenge to malaria elimination in Ethiopia, where P. vivax accounts for up to 40% of malaria infections. We report here occurrence of a total of 15 episodes of primaquine treatment failure for radical cure in three historical P. vivax malaria patients from Gambella, Ethiopia, during 8-16 months of follow-up in 1985-1987. The total primaquine doses received were 17.5 mg/kg, 25.8 mg/kg, and 35.8 mg/kg, respectively. These total doses are much higher than in previous reports of patients with treatment failure in Ethiopia and East Africa. The possibility of new infection was excluded for these cases as the treatment and follow-up were carried out in Addis Ababa, a malaria-free city. Recrudescences were unlikely, considering the short duration pattern of the recurrences. The cytochrome P450 2D6 (CYP2D6) status for these patients is unknown, but polymorphisms have been described in Ethiopia and may have contributed to primaquine treatment failures. It is suggested that further studies be carried out in Ethiopia to determine the prevalence and distribution of primaquine treatment failures in different ethnic groups, considering the impact of CYP2D6 polymorphisms and the potential value of increasing the primaquine dose to avoid relapse.

Factors influencing the uptake of voluntary HIV counseling and testing in rural Ethiopia: a cross sectional study.

BACKGROUND: Voluntary counseling and testing (VCT) has been one of the key policy responses to the HIV/AIDS epidemic in Ethiopia. However, the utilization of VCT has been low in the rural areas of the country. Understanding factors influencing the utilization of VCT provides information for the design of context based appropriate strategies that aim to improve utilization. This study examined the effects of socio-demographic and behavioral factors, and health service characteristics on the uptake of VCT among rural adults in Ethiopian. METHODS/DESIGN: This study was designed as a cross sectional study. Data from 11,919 adults (6278 women aged 15-49 years and 5641 men aged 15-59 years) residing in rural areas of Ethiopia who participated in a national health extension program evaluation were used for this study. The participants were selected from ten administrative regions using stratified multi-stage cluster sampling. Multivariate logistic regression analysis was performed accounting for factors associated with the use of VCT service. RESULTS: Overall, men (28 %) were relatively more likely to get tested for HIV than women (23.7 %) through VCT. Rural men and women who were young and better educated, who perceived having small risk of HIV infection, who had comprehensive knowledge, no stigmatization attitude and discussed about HIV/AIDS with their partner, and model-family were more likely to undergone VCT. Regional state was also strongly associated with VCT utilization in both men and women. Rural women who belonged to households with higher socio-economic status, non-farming occupation, female-headed household and located near health facility, and who visited health extension workers and participated in community conversation were more likely to use VCT. Among men, agrarian lifestyle was associated with VCT use. CONCLUSIONS: Utilization of VCT in the rural communities is low, and socio-economic, behavioral and health service factors influence its utilization. For increasing the utilization of VCT service in rural areas, there is a need to target the less educated, women, poor and farming families with a focus on improving knowledge and reducing HIV/AIDS related stigma. Strategy should include promoting partner and community conversations, accelerating model-family training, and using alternative modes of testing.

Use of Balanced Scorecard Methodology for Performance Measurement of the Health Extension Program in Ethiopia.

In 2004, Ethiopia introduced a community-based Health Extension Program to deliver basic and essential health services. We developed a comprehensive performance scoring methodology to assess the performance of the program. A balanced scorecard with six domains and 32 indicators was developed. Data collected from 1,014 service providers, 433 health facilities, and 10,068 community members sampled from 298 villages were used to generate weighted national, regional, and agroecological zone scores for each indicator. The national median indicator scores ranged from 37% to 98% with poor performance in commodity availability, workforce motivation, referral linkage, infection prevention, and quality of care. Indicator scores showed significant difference by region (P < 0.001). Regional performance varied across indicators suggesting that each region had specific areas of strength and deficiency, with Tigray and the Southern Nations, Nationalities and Peoples Region being the best performers while the mainly pastoral regions of Gambela, Afar, and Benishangul-Gumuz were the worst. The findings of this study suggest the need for strategies aimed at improving specific elements of the program and its performance in specific regions to achieve quality and equitable health services.

Human resource development for a community-based health extension program: a case study from Ethiopia.

INTRODUCTION: Ethiopia is one of the sub-Saharan countries most affected by high disease burden, aggravated by a shortage and imbalance of human resources, geographical distance, and socioeconomic factors. In 2004, the government introduced the Health Extension Program (HEP), a primary care delivery strategy, to address the challenges and achieve the World Health Organization Millennium Development Goals (MDGs) within a context of limited resources. CASE DESCRIPTION: The health system was reformed to create a platform for integration and institutionalization of the HEP with appropriate human capacity, infrastructure, and management structures. Human resources were developed through training of female health workers recruited from their prospective villages, designed to limit the high staff turnover and address gender, social and cultural factors in order to provide services acceptable to each community. The service delivery modalities include household, community and health facility care. Thus, the most basic health post infrastructure, designed to rapidly and cost-effectively scale up HEP, was built in each village. In line with the country's decentralized management system, the HEP service delivery is under the jurisdiction of the district authorities. DISCUSSION AND EVALUATION: The nationwide implementation of HEP progressed in line with its target goals. In all, 40 training institutions were established, and over 30,000 Health Extension Workers have been trained and deployed to approximately 15,000 villages. The potential health service coverage reached 92.1% in 2011, up from 64% in 2004. While most health indicators have improved, performance in skilled delivery and postnatal care has not been satisfactory. While HEP is considered the most important institutional framework for achieving the health MDGs in Ethiopia, quality of service, utilization rate, access and referral linkage to emergency obstetric care, management, and evaluation of the program are the key challenges that need immediate attention. CONCLUSIONS: This article describes the strategies, human resource developments, service delivery modalities, progress in service coverage, and the challenges in the implementation of the HEP. The Ethiopian approach of revitalization of primary care through innovative, locally appropriate and acceptable strategies will provide important lessons to other poorly resourced countries. It is hoped that the approaches and strategies described in this paper will aid in that process.

Physical condition of Olyset® nets after five years of utilization in rural western Kenya.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are a cornerstone of malaria control at present, and millions are used each day across the globe. However, there is limited information about the durability of LLINs under different conditions of utilization and there is no consensus about when a LLIN ceases to be protective due to physical deterioration. This knowledge is important for malaria control programmes to plan for procurement and replacement. METHODS: A cross-sectional survey of 208 households where Olyset® nets distributed five years ago were still present was conducted in the village of Sauri, western Kenya, in the context of the Millennium Villages Project. Information on bed net utilization and maintenance was collected in each household through a structured questionnaire, and one five-year-old Olyset® net from each sampled household was randomly selected and collected for physical examination. All holes larger than 0.5 cm were measured in each net, registering their position, and a hole index was calculated following WHO guidelines. Nets were classified as in good condition, moderately damaged or badly torn based on the hole index. The analysis explored the associations between demographic and socioeconomic characteristics of households, patterns of bed net utilization and maintenance and physical condition of the nets. Additional analysis was conducted using malaria prevalence data collected in a separate survey to explore if there was any association between the condition of the net collected in a household and the presence of malaria parasites in members of that household. RESULTS: 81.4% of Olyset® nets distributed five years ago were still present in the surveyed households, and 98.97% of the nets were reportedly used the previous night. Nets had an average of 34.2 holes (95% CI 30.12-38.22), and the mean hole index was 849 (95% CI 711-986), IQR 174-1,135. 15.2% of nets were still in good condition, 46.1% were moderately damaged and 38.7% were badly torn after five years of utilization. There was no association between household characteristics or patterns of bed net utilization or maintenance and physical condition of the nets. The only predictor of the physical condition of the net was the cleanliness at the time of examination. There was a difference of 17.6 percentage points in the proportion of households with at least one blood smear positive for Plasmodium falciparum between households with a net in good condition (5.3%) and those with a moderately damaged or badly torn net (22.9%), 95% CI (0.04-0.305), t=2.77 with unequal variance, p=0.009. CONCLUSIONS: Olyset® nets were used extensively in Sauri, western Kenya after five years of distribution, regardless of their physical condition. However, only 15% were found in good condition. Nets in good condition seem to be still protective after five years of utilization, while nets with more than 100 cm2 of holed surface may be associated with higher malaria parasitaemia at household level. Continued replacement of damaged nets and promotion of net maintenance and repair may be necessary to maintain the protective effectiveness of LLINs.

The effect of an integrated multisector model for achieving the Millennium Development Goals and improving child survival in rural sub-Saharan Africa: a non-randomised controlled assessment.

BACKGROUND: Simultaneously addressing multiple Millennium Development Goals (MDGs) has the potential to complement essential health interventions to accelerate gains in child survival. The Millennium Villages project is an integrated multisector approach to rural development operating across diverse sub-Saharan African sites. Our aim was to assess the effects of the project on MDG-related outcomes including child mortality 3 years after implementation and compare these changes to local comparison data. METHODS: Village sites averaging 35,000 people were selected from rural areas across diverse agroecological zones with high baseline levels of poverty and undernutrition. Starting in 2006, simultaneous investments were made in agriculture, the environment, business development, education, infrastructure, and health in partnership with communities and local governments at an annual projected cost of US$120 per person. We assessed MDG-related progress by monitoring changes 3 years after implementation across Millenium Village sites in nine countries. The primary outcome was the mortality rate of children younger than 5 years of age. To assess plausibility and attribution, we compared changes to reference data gathered from matched randomly selected comparison sites for the mortality rate of children younger than 5 years of age. Analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT01125618. FINDINGS: Baseline levels of MDG-related spending averaged $27 per head, increasing to $116 by year 3 of which $25 was spent on health. After 3 years, reductions in poverty, food insecurity, stunting, and malaria parasitaemia were reported across nine Millennium Village sites. Access to improved water and sanitation increased, along with coverage for many maternal-child health interventions. Mortality rates in children younger than 5 years of age decreased by 22% in Millennium Village sites relative to baseline (absolute decrease 25 deaths per 1000 livebirths, p=0·015) and 32% relative to matched comparison sites (30 deaths per 1000 livebirths, p=0·033). INTERPRETATION: An integrated multisector approach for addressing the MDGs can produce rapid declines in child mortality in the first 3 years of a long-term effort in rural sub-Saharan Africa. FUNDING: UN Human Security Trust Fund, the Lenfest Foundation, Bill & Melinda Gates Foundation, and Becton Dickinson.

Confirmed vivax resistance to chloroquine and effectiveness of artemether-lumefantrine for the treatment of vivax malaria in Ethiopia.

Chloroquine (CQ) is still the drug of choice for the treatment of vivax malaria in Ethiopia, whereas artemether-lumefantrine (AL) is for falciparum malaria. In this setting, clinical malaria cases are treated with AL. This necessitated the need to assess the effectiveness of AL for the treatment of Plasmodium vivax with CQ as a comparator. A total of 57 (80.3%) and 75 (85.2%) cases treated with CQ or AL, respectively, completed the study in an outpatient setting. At the end of the follow-up period of 28 days, a cumulative incidence of treatment failure of 7.5% (95% confidence interval [CI] = 2.9-18.9%) for CQ and 19% (95% CI = 11-31.6%) for AL was detected. CQ resistance was confirmed in three of five CQ treatment failures cases. The effectiveness of AL seems lower than CQ; however, the findings were not conclusive, because the AL evening doses were not supervised.

Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia.

Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P. vivax resistance to chloroquine and chloroquine plus primaquine treatment although these drugs have been used as the first line treatment for over 50 years. We assessed the efficacy of standard chloroquine and chloroquine plus primaquine treatment for P. vivax infections in a randomized open-label comparative study in Debre Zeit and Nazareth in East Shoa, Ethiopia. A total of 290 patients with microscopically confirmed P. vivax malaria who presented to the outpatient settings of the two laboratory centers were enrolled: 145 patients were randomized to receive CQ and 145 to receive CQ+PQ treatment. Participants were followed-up for 28-157 days according to the WHO procedures. There were 12 (6.5%) lost to follow-up patients and 9 (3.1%) withdrawals. In all, 96% (277/290) of patients were analysed at day 28. Baseline characteristics were similar in all treatment groups. In all, 98.6% (275/277) of patients had cleared their parasitemia on day 3 with no difference in mean parasite clearance time between regimens (48.34+/-17.68, 50.67+/-15.70 h for the CQ and CQ+PQ group, respectively, P=0.25). The cumulative incidence of therapeutic failure at day 28 by a life-table analysis method was 5.76% (95% CI: 2.2-14.61) and 0.75% (95% CI: 0.11-5.2%) in the CQ and CQ+PQ group, respectively (P=0.19). The relapse rate was 8% (9/108) for the CQ group and 3% (4/132) for the comparison group (P=0.07). The cumulative risk of relapse at day 157 by a life-table method was 61.8% (95% CI: 20.1-98.4%) in the CQ group, compared with 26.3% (95% CI: 7.5-29.4%) in the CQ+PQ group (P=0.0038). The study confirms the emergence of CQ and PQ resistance/treatment failure in P. vivax malaria in Ethiopia. Although treatment failures were detected, they were similar between the treatment groups. We recommend regular monitoring and periodic evaluation of the efficacy of these antimalarial drugs in systematically selected sentinel sites to detect further development of resistance and to make timely national antimalarial drug policy changes.

A temporal-spatial analysis of malaria transmission in Adama, Ethiopia.

Urban malaria is a growing problem in Africa. Small-scale spatial studies are useful in identifying foci of malaria transmission in urban communities. A population-based cohort study comprising 8,088 individuals was conducted in Adama, Ethiopia. During a single malaria season, the Kulldorff scan statistic identified one temporally stable spatial malaria cluster within 350 m of a major Anopheles breeding site. Factors associated with malaria incidence were residential proximity to vector breeding site, poor house condition (incidence rate ratio [IRR] = 2.0, 95% confidence interval [CI] = 1.4, 2.9), and a high level of vegetation (IRR = 1.8, 95% CI = 1.0, 3.3). Maximum (IRR = 1.4, 95% CI = 1.1, 1.9) and minimum daily temperatures (degrees C; IRR = 1.3, 95% CI = 1.2, 1.5) were positively associated with malaria incidence after a 1-month delay. Rainfall was positively associated with malaria incidence after a 10-day delay. Findings support the use of small scale mapping and targeted vector control in urban malaria control programs in Africa.

Individual and household level factors associated with malaria incidence in a highland region of Ethiopia: a multilevel analysis.

Multilevel analysis was used to identify individual and household level factors associated with malaria risk in 1,367 individuals in a peri-urban area of highland Ethiopia. Living within 450 m of a major vector-breeding site accounted for 38.78% and 78.49% of between-household variance in malaria incidence in adults and children, respectively. In adults, other individual level factors associated with malaria risk were regular or recent travel to rural areas (incidence rate ratio [IRR] = 12.96; 95% confidence interval [CI] = 4.05, 41.48) and having an indoor job (IRR = 0.37; 95% CI = 0.16, 0.87). Household level factors associated with adult malaria risk were low vegetation level in compound (IRR = 0.27; 95% CI = 0.10, 0.78), tidy compound (IRR = 0.29; 95% CI = 0.12, 0.71), household use of preventive measures (IRR = 0.31; 95% CI = 0.13, 0.74), and the number of 5- to 9-year-old children in the household (IRR = 1.66; 95% CI = 1.08, 2.53). Aside from distance to the vector-breeding site, few other malaria risk factors were identified in children. Malaria interventions in highland African communities should address household level factors associated with malaria clustering.

Malaria in São Tomé and principe: on the brink of elimination after three years of effective antimalarial measures.

In 2005, São Tomé e Príncipe began an initiative aimed at reducing malaria-related mortality to zero. The program included mass coverage with two antivector intervention methods (indoor residual spraying and long-lasting insecticidal nets), artemisinin-based combination therapy, and intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine. At the end of 2007, three years after intensified interventions began, malaria-attributed outpatient consultations, hospitalizations, and deaths decreased by more than 85%, 80%, and 95%, respectively, in all age groups. Mean prevalence of parasitemia and splenomegaly were also significantly reduced to 2.1% (P < 0.0001) and 0.3% (P < 0.0001) after two rounds of spraying from baseline prevalences of 30.5% and 48.8%, respectively. The dramatic reduction in malaria morbidity and mortality now enable serious consideration of new goals and strategies aimed at completely interrupting malaria transmission on these islands. We report evidence of the program's impact and the feasibility of and potential strategies for eliminating malaria from São Tomé e Príncipe.

Malaria and poverty.

Malaria is one of the most important challenges to global public health. African countries south of the Sahara bear today the heaviest burden of malaria. The relationship between poverty and malaria has long been recognized but its paths are multiple and complex. Recent studies suggest that causality works both ways, trapping communities in reinforcing cycles of poverty and disease. If malaria is to be controlled or eventually eliminated, the social and economic conditions that fuel malaria transmission need to be addressed. At the same time, malaria control should be seen as a poverty reduction strategy.

The African Millennium Villages.

We describe the concept, strategy, and initial results of the Millennium Villages Project and implications regarding sustainability and scalability. Our underlying hypothesis is that the interacting crises of agriculture, health, and infrastructure in rural Africa can be overcome through targeted public-sector investments to raise rural productivity and, thereby, to increased private-sector saving and investments. This is carried out by empowering impoverished communities with science-based interventions. Seventy-eight Millennium Villages have been initiated in 12 sites in 10 African countries, each representing a major agro-ecological zone. In early results, the research villages in Kenya, Ethiopia, and Malawi have reduced malaria prevalence, met caloric requirements, generated crop surpluses, enabled school feeding programs, and provided cash earnings for farm families.

Estimated global resources needed to attain international malaria control goals.

OBJECTIVE: To provide the international community with an estimate of the amount of financial resources needed to scale up malaria control to reach international goals, including allocations by country, year and intervention as well as an indication of the current funding gap. METHODS: A costing model was used to estimate the total costs of scaling up a set of widely recommended interventions, supporting services and programme strengthening activities in each of the 81 most heavily affected malaria-endemic countries. Two scenarios were evaluated, using different assumptions about the effect of interventions on the needs for diagnosis and treatment. Current health expenditures and funding for malaria control were compared to estimated needs. FINDINGS: A total of US$ 38 to 45 billion will be required from 2006 to 2015. The average cost during this period is US$ 3.8 to 4.5 billion per year. The average costs for Africa are US$ 1.7 billion and US$ 2.2 billion per year in the optimistic and pessimistic scenarios, respectively; outside Africa, the corresponding costs are US$ 2.1 billion and US$ 2.4 billion. CONCLUSION: While these estimates should not be used as a template for country-level planning, they provide an indication of the scale and scope of resources required and can help donors to collaborate towards meeting a global benchmark and targeting funding to countries in greatest need. The analysis highlights the need for much greater resources to achieve the goals and targets for malaria control set by the international community.

Scaling up malaria control in Africa: an economic and epidemiological assessment.

This paper estimates the number of people at risk of contracting malaria in Africa using GIS methods and the disease's epidemiologic characteristics. It then estimates yearly costs of covering the population at risk with the package of interventions (differing by level of malaria endemicity and differing for rural and urban populations) for malaria as recommended by the UN Millennium Project. These projected costs are calculated assuming a ramp-up of coverage to full coverage by 2008, and then projected out through 2015 to give a year-by-year cost of meeting the Millennium Development Goal for reducing the burden of malaria by 75%. We conclude that the cost of comprehensive malaria control for Africa is US $3.0 billion per year on average, or around US $4.02 per African at risk.

Rapid urban malaria appraisal (RUMA) in sub-Saharan Africa.

BACKGROUND: The rapid urban malaria appraisal (RUMA) methodology aims to provide a cost-effective tool to conduct rapid assessments of the malaria situation in urban sub-Saharan Africa and to improve the understanding of urban malaria epidemiology. METHODS: This work was done in Yopougon municipality (Abidjan), Cotonou, Dar es Salaam and Ouagadougou. The study design consists of six components: 1) a literature review, 2) the collection of available health statistics, 3) a risk mapping, 4) school parasitaemia surveys, 5) health facility-based surveys and 6) a brief description of the health care system. These formed the basis of a multi-country evaluation of RUMA's feasibility, consistency and usefulness. RESULTS: A substantial amount of literature (including unpublished theses and statistics) was found at each site, providing a good overview of the malaria situation. School and health facility-based surveys provided an overview of local endemicity and the overall malaria burden in different city areas. This helped to identify important problems for in-depth assessment, especially the extent to which malaria is over-diagnosed in health facilities. Mapping health facilities and breeding sites allowed the visualization of the complex interplay between population characteristics, health services and malaria risk. However, the latter task was very time-consuming and required special expertise. RUMA is inexpensive, costing around 8,500-13,000 USD for a six to ten-week period. CONCLUSION: RUMA was successfully implemented in four urban areas with different endemicity and proved to be a cost-effective first approach to study the features of urban malaria and provide an evidence basis for planning control measures.