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1.  Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial 
The Journal of Infectious Diseases  2016;214(12):1831-1839.
Background. Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.
Methods. A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence.
Results. All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02–.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06–1.49; P = .14) and 58% lower (0.42; .18–.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point.
Conclusions. Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.
Clinical Trials Registration. NCT02329301.
doi:10.1093/infdis/jiw416
PMCID: PMC5142084  PMID: 27923947
malaria; elimination; mass drug administration
2.  Linking household and facility data for better coverage measures in reproductive, maternal, newborn, and child health care: systematic review 
Journal of Global Health  null;6(2):020501.
Background
Currently many measures of intervention coverage obtained from household surveys do not measure actual health intervention/service delivery, resulting in a need for linking reports of care–seeking with assessments of the service environment in order to improve measurements. This systematic review aims to identify evidence of different methods used to link household surveys and service provision assessments, with a focus on reproductive, maternal, newborn and child health care, in low– and middle–income countries.
Methods
Using pre–defined search terms, articles published in peer–reviewed journals and the grey literature after 1990 were identified, their reference lists scanned and linking methods synthesized.
Findings
A total of 59 articles and conference presentations were carefully reviewed and categorized into two groups based on the linking method used: 1) indirect/ecological linking that included studies in which health care–seeking behavior was linked to all or the nearest facilities or providers of certain types within a geographical area, and 2) direct linking/exact matching where individuals were linked with the exact provider or facility where they sought care. The former approach was employed in 51 of 59 included studies, and was particularly common among studies that were based on independent sources of household and facility data that were nationally representative. Only eight of the 59 reviewed studies employed direct linking methods, which were typically done at the sub–national level (eg, district level) and often in rural areas, where the number of providers was more limited compared to urban areas.
Conclusions
Different linking methods have been reported in the literature, each category has its own set of advantages and limitations, in terms of both methodology and practicality for scale–up. Future studies that link household and provider/facility data should also take into account factors such as sources of data, the timing of surveys, the temporality of data points, the type of services and interventions, and the scale of the study in order to produce valid and reliable results.
doi:10.7189/jogh.06.020501
PMCID: PMC5012234  PMID: 27606060
3.  The relative contribution of climate variability and vector control coverage to changes in malaria parasite prevalence in Zambia 2006–2012 
Parasites & Vectors  2016;9:431.
Background
Four malaria indicator surveys (MIS) were conducted in Zambia between 2006 and 2012 to evaluate malaria control scale-up. Nationally, coverage of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) increased over this period, while parasite prevalence in children 1–59 months decreased dramatically between 2006 and 2008, but then increased from 2008 to 2010. We assessed the relative effects of vector control coverage and climate variability on malaria parasite prevalence over this period.
Methods
Nationally-representative MISs were conducted in April-June of 2006, 2008, 2010 and 2012 to collect household-level information on malaria control interventions such as IRS, ITN ownership and use, and child parasite prevalence by microscopic examination of blood smears. We fitted Bayesian geostatistical models to assess the association between IRS and ITN coverage and climate variability and malaria parasite prevalence. We created predictions of the spatial distribution of malaria prevalence at each time point and compared results of varying IRS, ITN, and climate inputs to assess their relative contributions to changes in prevalence.
Results
Nationally, the proportion of households owning an ITN increased from 37.8 % in 2006 to 64.3 % in 2010 and 68.1 % in 2012, with substantial heterogeneity sub-nationally. The population-adjusted predicted child malaria parasite prevalence decreased from 19.6 % in 2006 to 10.4 % in 2008, but rose to 15.3 % in 2010 and 13.5 % in 2012. We estimated that the majority of this prevalence increase at the national level between 2008 and 2010 was due to climate effects on transmission, although there was substantial heterogeneity at the provincial level in the relative contribution of changing climate and ITN availability. We predict that if climate factors preceding the 2010 survey were the same as in 2008, the population-adjusted prevalence would have fallen to 9.9 % nationally.
Conclusions
These results suggest that a combination of climate factors and reduced intervention coverage in parts of the country contributed to both the reduction and rebound in malaria parasite prevalence. Unusual rainfall patterns, perhaps related to moderate El Niño conditions, may have contributed to this variation. Zambia has demonstrated considerable success in scaling up vector control. This analysis highlights the importance of accounting for climate variability when using cross-sectional data for evaluation of malaria control efforts.
Electronic supplementary material
The online version of this article (doi:10.1186/s13071-016-1693-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s13071-016-1693-0
PMCID: PMC4974721  PMID: 27496161
Malaria; Climate; Vector control; Geostatistics
4.  Malaria vector research and control in Haiti: a systematic review 
Malaria Journal  2016;15:376.
Background
Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a systematic review of the literature on malaria vector research, bionomics and control in Haiti.
Methods
A systematic search of literature published in French, Spanish and English languages was conducted in 2015 using Pubmed (MEDLINE), Google Scholar, EMBASE, JSTOR WHOLIS and Web of Science databases as well other grey literature sources such as USAID, and PAHO. The following search terms were used: malaria, Haiti, Anopheles, and vector control.
Results
A total of 132 references were identified with 40 high quality references deemed relevant and included in this review. Six references dealt with mosquito distribution, seven with larval mosquito ecology, 16 with adult mosquito ecology, three with entomological indicators of malaria transmission, eight with insecticide resistance, one with sero-epidemiology and 16 with vector control. In the last 15 years (2000–2015), there have only been four published papers and three-scientific meeting abstracts on entomology for malaria in Haiti. Overall, the general literature on malaria vector research in Haiti is limited and dated.
Discussion
Entomological information generated from past studies in Haiti will contribute to the development of strategies to achieve malaria elimination on Hispaniola. However it is of paramount importance that malaria vector research in Haiti is updated to inform decision-making for vector control strategies in support of malaria elimination.
doi:10.1186/s12936-016-1436-x
PMCID: PMC4957415  PMID: 27443992
Haiti; Malaria; Anopheles; Vector control
5.  Coverage and system efficiencies of insecticide-treated nets in Africa from 2000 to 2017 
eLife  null;4:e09672.
Insecticide-treated nets (ITNs) for malaria control are widespread but coverage remains inadequate. We developed a Bayesian model using data from 102 national surveys, triangulated against delivery data and distribution reports, to generate year-by-year estimates of four ITN coverage indicators. We explored the impact of two potential 'inefficiencies': uneven net distribution among households and rapid rates of net loss from households. We estimated that, in 2013, 21% (17%–26%) of ITNs were over-allocated and this has worsened over time as overall net provision has increased. We estimated that rates of ITN loss from households are more rapid than previously thought, with 50% lost after 23 (20–28) months. We predict that the current estimate of 920 million additional ITNs required to achieve universal coverage would in reality yield a lower level of coverage (77% population access). By improving efficiency, however, the 920 million ITNs could yield population access as high as 95%.
DOI: http://dx.doi.org/10.7554/eLife.09672.001
eLife digest
Malaria is a major cause of death in many parts of the world, especially in sub-Saharan Africa. Recently, there has been a renewed emphasis on using preventive measures to reduce the deaths and illnesses caused by malaria. Insecticide-treated nets are the most prominent preventive measure used in areas where malaria is particularly common. However, despite huge international efforts to send enough nets to the regions that need them, the processes of delivering and distributing the nets are inefficient. This problem is compounded by the fact that little information is available on how many nets people actually own and use within each country.`
Bhatt et al. have now created a mathematical model that describes the use and distribution of nets across Africa since 2000. This is based on data collected from national surveys and reports on the delivery and distribution of the nets. The model estimates that in 2013, only 43% of people at risk of malaria slept under a net. Furthermore, 21% of new nets were allocated to households that already had enough nets, an inefficiency that has worsened over the years. Nets are also lost from households much more rapidly than previously thought.
It’s currently estimated that 920 million additional nets are required to ensure that everyone at risk from malaria in Africa is adequately protected. However, Bhatt et al.’s model suggests that given the current inefficiencies in net distribution, the extra nets would in reality protect a much smaller proportion of the population. Taking measures to more effectively target the nets to the households that need them could improve this coverage level to 95% of the population. The next challenge is to devise distribution strategies to send nets to where they are most needed.
DOI: http://dx.doi.org/10.7554/eLife.09672.002
doi:10.7554/eLife.09672
PMCID: PMC4758960  PMID: 26714109
ITN; LLIN; Bayesian compatment model; Malaria; Human
6.  Community Coverage with Insecticide-Treated Mosquito Nets and Observed Associations with All-Cause Child Mortality and Malaria Parasite Infections 
Randomized trials and mathematical modeling suggest that insecticide-treated mosquito nets (ITNs) provide community-level protection to both those using ITNs and those without individual access. Using nationally representative household survey datasets from 17 African countries, we examined whether community ITN coverage is associated with malaria infections in children < 5 years old and all-cause child mortality (ACCM) among children < 5 years old in households with one or more ITNs versus without any type of mosquito net (treated or untreated). Increasing ITN coverage (> 50%) was protective against malaria infections and ACCM for children in households with an ITN, although this protection was not conferred to children in households without ITNs in these data. Children in households with ITNs were protected against malaria infections and ACCM with ITN coverage > 30%, but this protection was not significant with ITN coverage < 30%. Results suggest that ITNs are more effective with higher ITN coverage.
doi:10.4269/ajtmh.14-0318
PMCID: PMC4228892  PMID: 25200267
7.  Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial 
Trials  2015;16:347.
Background
Mass drug administration (MDA) and focal MDA (fMDA) using dihydroartemisinin plus piperaquine (DHAp), represent two strategies to maximize the use of existing information to achieve greater clearance of human infection and reduce the parasite reservoir, and provide longer chemoprophylactic protection against new infections. The primary aim of this study is to quantify the relative effectiveness of MDA and fMDA with DHAp against no mass treatment (standard of care) for reducing Plasmodium falciparum prevalence and incidence.
Methods/design
The study will be conducted along Lake Kariba in Southern Province, Zambia; an area of low to moderate malaria transmission and high coverage of vector control. A community randomized controlled trial (CRCT) of 60 health facility catchment areas (HFCAs) will be used to evaluate the impact of two rounds of MDA and fMDA interventions, relative to a control of no mass treatment, stratified by high and low transmission. Community residents in MDA HFCAs will be treated with DHAp at the end of the dry season (round one: November to December 2014) and the beginning of the rainy season (round two: February to March 2015). Community residents in fMDA HFCAs will be tested during the same two rounds for malaria parasites with a rapid diagnostic test; all positive individuals and all individuals living in their household will be treated with DHAp. Primary outcomes include malaria parasite prevalence (n = 5,640 children aged one month to under five-years-old), as measured by pre- and post-surveys, and malaria parasite infection incidence (n = 2,250 person-years among individuals aged three months and older), as measured by a monthly longitudinal cohort. The study is powered to detect approximately a 50 % relative reduction in these outcomes between each intervention group versus the control.
Discussion
Strengths of this trial include: a robust study design (CRCT); cross-sectional parasite surveys as well as a longitudinal cohort; and stratification of high and low transmission areas. Primary limitations include: statistical power to detect only a 50 % reduction in primary outcomes within high and low transmission strata; potential for contamination; and potential for misclassification of exposure.
Trial registration
Identifier: Clinicaltrials.gov: NCT02329301. Registration date: 30 December 2014.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-015-0862-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-015-0862-3
PMCID: PMC4535296  PMID: 26268804
Malaria; Mass drug administration; Dihydroartemisinin plus piperaquine
8.  Costs and cost-effectiveness of a large-scale mass testing and treatment intervention for malaria in Southern Province, Zambia 
Malaria Journal  2015;14:211.
Background
A cluster, randomized, control trial of three dry-season rounds of a mass testing and treatment intervention (MTAT) using rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) was conducted in four districts in Southern Province, Zambia.
Methods
Data were collected on the costs and logistics of the intervention and paired with effectiveness estimated from a community randomized control trial for the purpose of conducting a provider perspective cost-effectiveness analysis of MTAT vs no MTAT (Standard of Care).
Results
Dry-season MTAT in this setting did not reduce malaria transmission sufficiently to permit transition to a case-investigation strategy to then pursue malaria elimination, however, the intervention did substantially reduce malaria illness and was a highly cost-effective intervention for malaria burden reduction in this moderate transmission area. The cost per RDT administered was estimated to be USD4.39 (range: USD1.62-13.96) while the cost per AL treatment administered was estimated to be USD34.74 (range: USD3.87-3,835). The net cost per disability adjusted life year averted (incremental cost-effectiveness ratio) was estimated to be USD804.
Conclusions
The intervention appears to be highly cost-effective relative to World Health Organization thresholds for malaria burden reduction in Zambia as compared to no MTAT. However, it was estimated that population-wide mass drug administration is likely to be more cost-effective for burden reduction and for transmission reduction compared to MTAT.
doi:10.1186/s12936-015-0722-3
PMCID: PMC4490652  PMID: 25985992
Malaria; Cost-effectiveness; Mass testing and treatment
9.  Population-Wide Malaria Testing and Treatment with Rapid Diagnostic Tests and Artemether-Lumefantrine in Southern Zambia: A community Randomized Step-Wedge Control Trial Design 
Reducing the human reservoir of malaria parasites is critical for elimination. We conducted a community randomized controlled trial in Southern Province, Zambia to assess the impact of three rounds of a mass test and treatment (MTAT) intervention on malaria prevalence and health facility outpatient case incidence using random effects logistic regression and negative binomial regression, respectively. Following the intervention, children in the intervention group had lower odds of a malaria infection than individuals in the control group (adjusted odds ratio = 0.47, 95% confidence interval [CI] = 0.24–0.90). Malaria outpatient case incidence decreased 17% in the intervention group relative to the control group (incidence rate ratio = 0.83, 95% CI = 0.68–1.01). Although a single year of MTAT reduced malaria prevalence and incidence, the impact of the intervention was insufficient to reduce transmission to a level approaching elimination where a strategy of aggressive case investigations could be used. Mass drug administration, more sensitive diagnostics, and gametocidal drugs may potentially improve interventions targeting the human reservoir of malaria parasites.
doi:10.4269/ajtmh.14-0347
PMCID: PMC4426577  PMID: 25802434
10.  A qualitative study of perceptions of a mass test and treat campaign in Southern Zambia and potential barriers to effectiveness 
Malaria Journal  2015;14:171.
Background
A mass test and treat campaign (MTAT) using rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) was conducted in Southern Zambia in 2012 and 2013 to reduce the parasite reservoir and progress towards malaria elimination. Through this intervention, community health workers (CHWs) tested all household members with rapid diagnostic tests (RDTs) and provided treatment to those that tested positive.
Methods
A qualitative study was undertaken to understand CHW and community perceptions regarding the MTAT campaign. A total of eight focus groups and 33 in-depth and key informant interviews were conducted with CHWs, community members and health centre staff that participated in the MTAT.
Results
Interviews and focus groups with CHWs and community members revealed that increased knowledge of malaria prevention, the ability to reach people who live far from health centres, and the ability of the MTAT campaign to reduce the malaria burden were the greatest perceived benefits of the campaign. Conversely, the primary potential barriers to effectiveness included refusals to be tested, limited adherence to drug regimens, and inadequate commodity supply. Study respondents generally agreed that MTAT services were scalable outside of the study area but would require greater involvement from district and provincial medical staff.
Conclusions
These findings highlight the importance of increased community sensitization as part of mass treatment campaigns for improving campaign coverage and acceptance. Further, they suggest that communication channels between the Ministry of Health, National Malaria Control Centre and Medical Stores Limited may need to be improved so as to ensure there is consistent supply and management of commodities. Continued capacity building of CHWs and health facility supervisors is critical for a more effective programme and sustained progress towards malaria elimination.
doi:10.1186/s12936-015-0686-3
PMCID: PMC4426174  PMID: 25896068
Mass Test and Treat; Malaria elimination; Qualitative methods
11.  A methodological framework for the improved use of routine health system data to evaluate national malaria control programs: evidence from Zambia 
Background
Due to challenges in laboratory confirmation, reporting completeness, timeliness, and health access, routine incidence data from health management information systems (HMIS) have rarely been used for the rigorous evaluation of malaria control program scale-up in Africa.
Methods
We used data from the Zambia HMIS for 2009–2011, a period of rapid diagnostic and reporting scale-up, to evaluate the association between insecticide-treated net (ITN) program intensity and district-level monthly confirmed outpatient malaria incidence using a dose–response national platform approach with district-time units as the unit of analysis. A Bayesian geostatistical model was employed to estimate longitudinal district-level ITN coverage from household survey and programmatic data, and a conditional autoregressive model (CAR) was used to impute missing HMIS data. The association between confirmed malaria case incidence and ITN program intensity was modeled while controlling for known confounding factors, including climate variability, reporting, testing, treatment-seeking, and access to health care, and additionally accounting for spatial and temporal autocorrelation.
Results
An increase in district level ITN coverage of one ITN per household was associated with an estimated 27% reduction in confirmed case incidence overall (incidence rate ratio (IRR): 0 · 73, 95% Bayesian Credible Interval (BCI): 0 · 65–0 · 81), and a 41% reduction in areas of lower malaria burden.
Conclusions
When improved through comprehensive parasitologically confirmed case reporting, HMIS data can become a valuable tool for evaluating malaria program scale-up. Using this approach we provide further evidence that increased ITN coverage is associated with decreased malaria morbidity and use of health services for malaria illness in Zambia. These methods and results are broadly relevant for malaria program evaluations currently ongoing in sub-Saharan Africa, especially as routine confirmed case data improve.
Electronic supplementary material
The online version of this article (doi:10.1186/s12963-014-0030-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12963-014-0030-0
PMCID: PMC4247605  PMID: 25435815
Malaria; Evaluation; Integrated Nested Laplace Approximation (INLA); Insecticide-treated nets; Health management information systems (HMIS)
13.  Monitoring, characterization and control of chronic, symptomatic malaria infections in rural Zambia through monthly household visits by paid community health workers 
Malaria Journal  2014;13:128.
Background
Active, population-wide mass screening and treatment (MSAT) for chronic Plasmodium falciparum carriage to eliminate infectious reservoirs of malaria transmission have proven difficult to apply on large national scales through trained clinicians from central health authorities.
Methodology
Fourteen population clusters of approximately 1,000 residents centred around health facilities (HF) in two rural Zambian districts were each provided with three modestly remunerated community health workers (CHWs) conducting active monthly household visits to screen and treat all consenting residents for malaria infection with rapid diagnostic tests (RDT). Both CHWs and HFs also conducted passive case detection among residents who self-reported for screening and treatment.
Results
Diagnostic positivity was higher among symptomatic patients self-reporting to CHWs (42.5%) and HFs (24%) than actively screened residents (20.3%), but spatial and temporal variations of diagnostic positivity were highly consistent across all three systems. However, most malaria infections (55.6%) were identified through active home visits by CHWs rather than self-reporting to CHWs or HFs. Most (62%) malaria infections detected actively by CHWs reported one or more symptoms of illness. Most reports of fever and vomiting, plus more than a quarter of history of fever, headache and diarrhoea, were attributable to malaria infection. The minority of residents who participated >12 times had lower rates of malaria infection and associated symptoms in later contacts but most residents were tested <4 times and high malaria diagnostic positivity (32%) in active surveys, as well as incidence (1.7 detected infections per person per year) persisted in the population. Per capita cost for active service delivery by CHWs was US$5.14 but this would rise to US$10.68 with full community compliance with monthly testing at current levels of transmission, and US$6.25 if pre-elimination transmission levels and negligible treatment costs were achieved.
Conclusion
Monthly active home visits by CHWs equipped with RDTs were insufficient to eliminate the human infection reservoir in this typical African setting, despite reasonably high LLIN/IRS coverage. However, dramatic impact upon infection and morbidity burden might be attainable and cost-effective if community participation in regular testing could be improved and the substantial, but not necessarily prohibitive, costs are affordable to national programmes.
doi:10.1186/1475-2875-13-128
PMCID: PMC4113135  PMID: 24678631
Malaria; Community health worker; Surveillance; Passive and active case detection; Treatment with ACT; Rapid diagnostic tests
14.  Declining malaria in Africa: improving the measurement of progress 
Malaria Journal  2014;13:39.
The dramatic escalation of malaria control activities in Africa since the year 2000 has increased the importance of accurate measurements of impact on malaria epidemiology and burden. This study presents a systematic review of the emerging published evidence base on trends in malaria risk in Africa and argues that more systematic, timely, and empirically-based approaches are urgently needed to track the rapidly evolving landscape of transmission.
doi:10.1186/1475-2875-13-39
PMCID: PMC3930350  PMID: 24479555
15.  Characterization of the Recombinant Exopeptidases PepX and PepN from Lactobacillus helveticus ATCC 12046 Important for Food Protein Hydrolysis 
PLoS ONE  2013;8(7):e70055.
The proline-specific X-prolyl dipeptidyl aminopeptidase (PepX; EC 3.4.14.11) and the general aminopeptidase N (PepN; EC 3.4.11.2) from Lactobacillus helveticus ATCC 12046 were produced recombinantly in E. coli BL21(DE3) via bioreactor cultivation. The maximum enzymatic activity obtained for PepX was 800 µkatH-Ala-Pro-pNA L−1, which is approx. 195-fold higher than values published previously. To the best of our knowledge, PepN was expressed in E. coli at high levels for the first time. The PepN activity reached 1,000 µkatH-Ala-pNA L−1. After an automated chromatographic purification, both peptidases were biochemically and kinetically characterized in detail. Substrate inhibition of PepN and product inhibition of both PepX and PepN were discovered for the first time. An apo-enzyme of the Zn2+-dependent PepN was generated, which could be reactivated by several metal ions in the order of Co2+>Zn2+>Mn2+>Ca2+>Mg2+. PepX and PepN exhibited a clear synergistic effect in casein hydrolysis studies. Here, the relative degree of hydrolysis (rDH) was increased by approx. 132%. Due to the remarkable temperature stability at 50°C and the complementary substrate specificities of both peptidases, a future application in food protein hydrolysis might be possible.
doi:10.1371/journal.pone.0070055
PMCID: PMC3716637  PMID: 23894590
16.  Planning long lasting insecticide treated net campaigns: should households’ existing nets be taken into account? 
Parasites & Vectors  2013;6:174.
Background
Mass distribution of long-lasting insecticide treated bed nets (LLINs) has led to large increases in LLIN coverage in many African countries. As LLIN ownership levels increase, planners of future mass distributions face the challenge of deciding whether to ignore the nets already owned by households or to take these into account and attempt to target individuals or households without nets. Taking existing nets into account would reduce commodity costs but require more sophisticated, and potentially more costly, distribution procedures. The decision may also have implications for the average age of nets in use and therefore on the maintenance of universal LLIN coverage over time.
Methods
A stochastic simulation model based on the NetCALC algorithm was used to determine the scenarios under which it would be cost saving to take existing nets into account, and the potential effects of doing so on the age profile of LLINs owned. The model accounted for variability in timing of distributions, concomitant use of continuous distribution systems, population growth, sampling error in pre-campaign coverage surveys, variable net ‘decay’ parameters and other factors including the feasibility and accuracy of identifying existing nets in the field.
Results
Results indicate that (i) where pre-campaign coverage is around 40% (of households owning at least 1 LLIN), accounting for existing nets in the campaign will have little effect on the mean age of the net population and (ii) even at pre-campaign coverage levels above 40%, an approach that reduces LLIN distribution requirements by taking existing nets into account may have only a small chance of being cost-saving overall, depending largely on the feasibility of identifying nets in the field. Based on existing literature the epidemiological implications of such a strategy is likely to vary by transmission setting, and the risks of leaving older nets in the field when accounting for existing nets must be considered.
Conclusions
Where pre-campaign coverage levels established by a household survey are below 40% we recommend that planners do not take such LLINs into account and instead plan a blanket mass distribution. At pre-campaign coverage levels above 40%, campaign planners should make explicit consideration of the cost and feasibility of accounting for existing LLINs before planning blanket mass distributions. Planners should also consider restricting the coverage estimates used for this decision to only include nets under two years of age in order to ensure that old and damaged nets do not compose too large a fraction of existing net coverage.
doi:10.1186/1756-3305-6-174
PMCID: PMC3689647  PMID: 23763773
Bed net; Long lasting insecticide treated bed net (LLIN); Malaria; Coverage; Mass campaign; Cost savings
17.  Measuring Coverage in MNCH: Accuracy of Measuring Diagnosis and Treatment of Childhood Malaria from Household Surveys in Zambia 
PLoS Medicine  2013;10(5):e1001417.
Background
To assess progress in the scale-up of rapid diagnostic tests and artemisinin-based combination therapies (ACTs) across Africa, malaria control programs have increasingly relied on standardized national household surveys to determine the proportion of children with a fever in the past 2 wk who received an effective antimalarial within 1–2 d of the onset of fever. Here, the validity of caregiver recall for measuring the primary coverage indicators for malaria diagnosis and treatment of children <5 y old is assessed.
Methods and Findings
A cross-sectional study was conducted in five public clinics in Kaoma District, Western Provence, Zambia, to estimate the sensitivity, specificity, and accuracy of caregivers' recall of malaria testing, diagnosis, and treatment, compared to a gold standard of direct observation at the health clinics. Compared to the gold standard of clinic observation, for recall for children with fever in the past 2 wk, the sensitivity for recalling that a finger/heel stick was done was 61.9%, with a specificity of 90.0%. The sensitivity and specificity of caregivers' recalling a positive malaria test result were 62.4% and 90.7%, respectively. The sensitivity and specificity of recalling that the child was given a malaria diagnosis, irrespective of whether a laboratory test was actually done, were 76.8% and 75.9%, respectively. The sensitivity and specificity for recalling that an ACT was given were 81.0% and 91.5%, respectively.
Conclusions
Based on these findings, results from household surveys should continue to be used for ascertaining the coverage of children with a fever in the past 2 wk that received an ACT. However, as recall of a malaria diagnosis remains suboptimal, its use in defining malaria treatment coverage is not recommended.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The World Health Organization estimates that there are over 200 million cases of malaria each year, with nearly 1 million deaths. The majority of these deaths are among children living in sub-Saharan Africa, and Plasmodium falciparum is the parasite responsible. Malaria transmission can be prevented by insect control measures, and current treatment regimens use antimalarial drugs. Recently, the use of highly effective artemisinin-based combination treatments (ACTs) has significantly reduced the deaths and disability caused by malaria. To avoid drug overuse and the development of parasite resistance to ACTs, the World Health Organization recommends that before treatment with ACTs, a laboratory test to confirm malaria should be performed. Rapid diagnostic tests (RDTs) allow health workers to diagnose malaria in settings lacking laboratory facilities, thus providing a method for improving malaria diagnosis and reducing the overuse of ACTs.
Why Was This Study Done?
The success of RDTs and ACTs across Africa in combating malaria is measured by standardized national household surveys. These surveys assess the proportion of children with a fever in the past two weeks who have received an antimalarial treatment within 1–2 days of the onset of fever. The surveys do not distinguish between treatment of a suspected malaria case and one that was laboratory confirmed. Due to the availability and scale-up of RDTs in many African countries, caregivers and mothers are also now asked in national surveys if the child was tested for malaria, but are not usually asked for the result of any malaria diagnostic test given. Knowing whether a child has been diagnosed with malaria is necessary to construct a better indicator of what proportion of children receive an effective and appropriate antimalarial within the appropriate treatment time frame. This indicator is important because it provides more insight into the current diagnosis and treatment policies in most African countries.
Biased coverage estimates for diagnosis and treatment may result from these types of surveys because survey questions to caregivers of children concerning fever in the past two weeks, treatment-seeking behavior, and malaria diagnosis and treatment can be particularly subject to sources of error and bias. Despite this possibility, these indicators and surveys have not been checked against direct observation of the children to assess the validity of caregivers' recall and household surveys to gauge appropriate treatment of malaria in children.
What Did the Researchers Do and Find?
In this study, the authors investigated the validity of caregiver recall of malaria diagnosis and treatment in children under five years old. The authors did a cross-sectional study of five public clinics in Kaoma District, Western Provence, Zambia, to estimate the sensitivity, specificity, and accuracy of caregivers' recall of malaria testing, malaria diagnosis, and antimalarial treatment, and compared the surveys to direct observation at the health clinics. The results from this study demonstrate low sensitivity of caregiver recall of malaria diagnostic use, test results, and malaria diagnosis among children who had a fever in the past two weeks. However, the accuracy of caregiver recall that a child received an ACT was relatively high in this setting. This suggests that the current indicator for measuring the coverage of children with a fever in the past two weeks who received an ACT can be applied in similar settings, and may be useful for estimating infection and treatment over time.
What Do These Findings Mean?
These findings suggest that results from household surveys are accurate for obtaining information about the coverage of children with a fever in the past two weeks that receive an ACT. However, as caregiver recall of a malaria diagnosis is not highly sensitive, the authors suggest that malaria diagnosis from caregiver recall in household surveys is not recommended for defining malaria treatment coverage.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001417.
More information about malaria is available from MedlinePlus, the World Health Organization, and the US Centers for Disease Control and Prevention
The Roll Back Malaria Partnership brings numerous organizations together to combat malaria around the globe
doi:10.1371/journal.pmed.1001417
PMCID: PMC3646207  PMID: 23667337
18.  Measuring Coverage in MNCH: Total Survey Error and the Interpretation of Intervention Coverage Estimates from Household Surveys 
PLoS Medicine  2013;10(5):e1001386.
In a PLOS Medicine Review, Thomas Eisele and colleagues discuss the importance of considering sampling and non-sampling errors when interpreting estimates of coverage of maternal, newborn, and child health interventions based on data from household surveys.
Nationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used.
doi:10.1371/journal.pmed.1001386
PMCID: PMC3646211  PMID: 23667331
19.  Travel history and malaria infection risk in a low-transmission setting in Ethiopia: a case control study 
Malaria Journal  2013;12:33.
Background
Malaria remains the leading communicable disease in Ethiopia, with around one million clinical cases of malaria reported annually. The country currently has plans for elimination for specific geographic areas of the country. Human movement may lead to the maintenance of reservoirs of infection, complicating attempts to eliminate malaria.
Methods
An unmatched case–control study was conducted with 560 adult patients at a Health Centre in central Ethiopia. Patients who received a malaria test were interviewed regarding their recent travel histories. Bivariate and multivariate analyses were conducted to determine if reported travel outside of the home village within the last month was related to malaria infection status.
Results
After adjusting for several known confounding factors, travel away from the home village in the last 30 days was a statistically significant risk factor for infection with Plasmodium falciparum (AOR 1.76; p=0.03) but not for infection with Plasmodium vivax (AOR 1.17; p=0.62). Male sex was strongly associated with any malaria infection (AOR 2.00; p=0.001).
Conclusions
Given the importance of identifying reservoir infections, consideration of human movement patterns should factor into decisions regarding elimination and disease prevention, especially when targeted areas are limited to regions within a country.
doi:10.1186/1475-2875-12-33
PMCID: PMC3570338  PMID: 23347703
Malaria; Travel; Human movement; Importation; Plasmodium vivax; Plasmodium falciparum; Ethiopia; Reservoir infection
20.  A quasi-experimental evaluation of an interpersonal communication intervention to increase insecticide-treated net use among children in Zambia 
Malaria Journal  2012;11:313.
Background
This paper presents results from an evaluation of the effect of a community health worker (CHW) –based, interpersonal communication campaign (IPC) for increasing insecticide-treated mosquito net (ITN) use among children in Luangwa District, Zambia, an area with near universal coverage of ITNs and moderate to low malaria parasite prevalence.
Methods
A quasi-experimental community randomized control trial was conducted from 2008 to 2010. CHWs were the unit of randomization. Cross-sectional data were collected from houses in both 2008 and 2010 using simple random sampling of a complete household enumeration of the district. A difference-in -differences approach was used to analyse the data.
Results
ITN use among children <5 years old in households with ≥1 ITN increased overall from 54% in 2008 to 81% in 2010 (χ2 = 96.3, p <0.01); however, there was no difference in increase between the treatment and control arms in 2010 (p >0.05). ITN use also increased among children five to 14 years old from 37% in 2008 to 68% in 2010. There was no indication that the CHW-based intervention activities had a significant effect on increasing ITN use in this context, over and above what is already being done to disseminate information on the importance of using an ITN to prevent malaria infection.
Discussion
ITN use increased dramatically in the district between 2008 and 2010. It is likely that IPC activities in general may have contributed to the observed increase in ITN use, as the increased observed in this study was far higher than the increase observed between 2008 and 2010 malaria indicator survey (MIS) estimates. Contamination across control communities, coupled with linear settlement patterns and subsequent behavioural norms related to communication in the area, likely contributed to the observed increase in net use and null effect in this study.
doi:10.1186/1475-2875-11-313
PMCID: PMC3459708  PMID: 22958441
Evaluation; Insecticide-treated net (ITN); Interpersonal communication campaign (IPC); Community health worker (CHW); Malaria; Zambia
21.  Reductions in Artemisinin-Based Combination Therapy Consumption after the Nationwide Scale up of Routine Malaria Rapid Diagnostic Testing in Zambia 
The National Malaria Control Center of Zambia introduced rapid diagnostic tests (RDTs) to detect Plasmodium falciparum as a pilot in some districts in 2005 and 2006; scale up at a national level was achieved in 2009. Data on RDT use, drug consumption, and diagnostic results were collected in three Zambian health districts to determine the impact RDTs had on malaria case management over the period 2004–2009. Reductions were seen in malaria diagnosis and antimalarial drug prescription (66.1 treatments per facility-month (95% confidence interval [CI] = 44.7–87.4) versus 26.6 treatments per facility-month (95% CI = 11.8–41.4)) pre- and post-RDT introduction. Results varied between districts, with significant reductions in low transmission areas but none in high areas. Rapid diagnostic tests may contribute to rationalization of treatment of febrile illness and reduce antimalarial drug consumption in Africa; however, their impact may be greater in lower transmission areas. National scale data will be necessary to confirm these findings.
doi:10.4269/ajtmh.2012.12-0127
PMCID: PMC3435345  PMID: 22848096
22.  Estimating Plasmodium falciparum Transmission Rates in Low-Endemic Settings Using a Combination of Community Prevalence and Health Facility Data 
PLoS ONE  2012;7(8):e42861.
As some malaria control programs shift focus from disease control to transmission reduction, there is a need for transmission data to monitor progress. At lower levels of transmission, it becomes increasingly more difficult to measure precisely, for example through entomological studies. Many programs conduct regular cross sectional parasite prevalence surveys, and have access to malaria treatment data routinely collected by ministries of health, often in health management information systems. However, by themselves, these data are poor measures of transmission. In this paper, we propose an approach for combining annual parasite incidence and treatment data with cross-sectional parasite prevalence and treatment seeking survey data to estimate the incidence of new infections in the human population, also known as the force of infection. The approach is based on extension of a reversible catalytic model. The accuracy of the estimates from this model appears to be highly dependent on levels of detectability and treatment in the community, indicating the importance of information on private sector treatment seeking and access to effective and appropriate treatment.
doi:10.1371/journal.pone.0042861
PMCID: PMC3425560  PMID: 22936995
23.  Production, active staining and gas chromatography assay analysis of recombinant aminopeptidase P from Lactococcus lactis ssp. lactis DSM 20481 
AMB Express  2012;2:39.
The aminopeptidase P (PepP, EC 3.4.11.9) gene from Lactococcus lactis ssp. lactis DSM 20481 was cloned, sequenced and expressed recombinantly in E. coli BL21 (DE3) for the first time. PepP is involved in the hydrolysis of proline-rich proteins and, thus, is important for the debittering of protein hydrolysates. For accurate determination of PepP activity, a novel gas chromatographic assay was established. The release of L-leucine during the hydrolysis of L-leucine-L-proline-L-proline (LPP) was examined for determination of PepP activity. Sufficient recombinant PepP production was achieved via bioreactor cultivation at 16 °C, resulting in PepP activity of 90 μkatLPP Lculture-1. After automated chromatographic purification by His-tag affinity chromatography followed by desalting, PepP activity of 73.8 μkatLPP Lculture-1 was achieved. This was approximately 700-fold higher compared to the purified native PepP produced by Lactococcus lactis ssp. lactis NCDO 763 as described in literature. The molecular weight of PepP was estimated to be ~ 40 kDa via native-PAGE together with a newly developed activity staining method and by SDS-PAGE. Furthermore, the kinetic parameters Km and Vmax were determined for PepP using three different tripeptide substrates. The purified enzyme showed a pH optimum between 7.0 and 7.5, was most active between 50°C and 60°C and exhibited reasonable stability at 0°C, 20°C and 37°C over 15 days. PepP activity could be increased 6-fold using 8.92 mM MnCl2 and was inhibited by 1,10-phenanthroline and EDTA.
doi:10.1186/2191-0855-2-39
PMCID: PMC3418211  PMID: 22853547
Lactococcus lactis; Aminopeptidase P; PepP; Gas chromatographic assay; Activity staining; LPP
24.  Household Possession and Use of Insecticide-Treated Mosquito Nets in Sierra Leone 6 Months after a National Mass-Distribution Campaign 
PLoS ONE  2012;7(5):e37927.
Background
In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country.
Methods
We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models.
Results
The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥1∶2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN.
Conclusions
The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.
doi:10.1371/journal.pone.0037927
PMCID: PMC3362537  PMID: 22666414
25.  Estimates of child deaths prevented from malaria prevention scale-up in Africa 2001-2010 
Malaria Journal  2012;11:93.
Background
Funding from external agencies for malaria control in Africa has increased dramatically over the past decade resulting in substantial increases in population coverage by effective malaria prevention interventions. This unprecedented effort to scale-up malaria interventions is likely improving child survival and will likely contribute to meeting Millennium Development Goal (MDG) 4 to reduce the < 5 mortality rate by two thirds between 1990 and 2015.
Methods
The Lives Saved Tool (LiST) model was used to quantify the likely impact that malaria prevention intervention scale-up has had on malaria mortality over the past decade (2001-2010) across 43 malaria endemic countries in sub-Saharan African. The likely impact of ITNs and malaria prevention interventions in pregnancy (intermittent preventive treatment [IPTp] and ITNs used during pregnancy) over this period was assessed.
Results
The LiST model conservatively estimates that malaria prevention intervention scale-up over the past decade has prevented 842,800 (uncertainty: 562,800-1,364,645) child deaths due to malaria across 43 malaria-endemic countries in Africa, compared to a baseline of the year 2000. Over the entire decade, this represents an 8.2% decrease in the number of malaria-caused child deaths that would have occurred over this period had malaria prevention coverage remained unchanged since 2000. The biggest impact occurred in 2010 with a 24.4% decrease in malaria-caused child deaths compared to what would have happened had malaria prevention interventions not been scaled-up beyond 2000 coverage levels. ITNs accounted for 99% of the lives saved.
Conclusions
The results suggest that funding for malaria prevention in Africa over the past decade has had a substantial impact on decreasing child deaths due to malaria. Rapidly achieving and then maintaining universal coverage of these interventions should be an urgent priority for malaria control programmes in the future. Successful scale-up in many African countries will likely contribute substantially to meeting MDG 4, as well as succeed in meeting MDG 6 (Target 1) to halt and reverse malaria incidence by 2015.
doi:10.1186/1475-2875-11-93
PMCID: PMC3350413  PMID: 22455864

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