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Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia
Malaria Journal volume 17, Article number: 220 (2018)
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Reactive case detection (RACD) is an active case finding strategy where households and neighbours of a passively identified case (index case) are screened to identify and treat additional malaria infections with the goal of gathering surveillance information and potentially reducing further transmission. Although it is widely considered a key strategy in low burden settings, little is known about the costs and the cost-effectiveness of different diagnostic methods used for RACD. The aims of this study were to measure the cost of conducting RACD and compare the cost-effectiveness of microscopy to the more sensitive diagnostic method loop-mediated isothermal amplification (LAMP).
The study was conducted in RACD surveillance sites in five sub-districts in Aceh Besar, Indonesia. The cost inputs and yield of implementing RACD with microscopy and/or LAMP were collected prospectively over a 20 months study period between May 2014 and December 2015. Costs and cost-effectiveness (USD) of the different strategies were examined. The main cost measures were cost per RACD event, per person screened, per population at risk (PAR); defined as total population in each sub-district, and per infection found. The main cost-effectiveness measure was incremental cost-effectiveness ratio (ICER), expressed as cost per malaria infection detected by LAMP versus microscopy. The effects of varying test positivity rate or diagnostic yield on cost per infection identified and ICER were also assessed.
Among 1495 household members and neighbours screened in 36 RACD events, two infections were detected by microscopy and confirmed by LAMP, and four infections were missed by microscopy but detected by LAMP. The average total cost of conducting RACD using microscopy and LAMP was $1178 per event with LAMP-specific consumables and personnel being the main cost drivers. The average cost of screening one individual during RACD was $11, with an additional cost of diagnostics at $0.62 and $16 per person for microscopy and LAMP, respectively. As a public health intervention, RACD using both diagnostics cost an average of $0.42 per PAR per year. Comparing RACD using microscopy only versus RACD using LAMP only, the cost per infection found was $8930 and $6915, respectively. To add LAMP as an additional intervention accompanying RACD would cost $9 per individual screened annually in this setting. The ICER was estimated to be $5907 per additional malaria infection detected by LAMP versus microscopy. Cost per infection identified and ICER declined with increasing test positivity rate and increasing diagnostic yield.
This study provides the first estimates on the cost and cost-effectiveness of RACD from a low transmission setting. Costs per individual screened were high, though costs per PAR were low. Compared to microscopy, the use of LAMP in RACD was more costly but more cost-effective for the detection of infections, with diminishing returns observed when findings were extrapolated to scenarios with higher prevalence of infection using more sensitive diagnostics. As malaria programmes consider active case detection and the integration of more sensitive diagnostics, these findings may inform strategic and budgetary planning.
Malaria transmission in low endemic areas tends to cluster geographically and temporally. Also, in low transmission settings, a higher proportion of infected individuals is asymptomatic, and therefore will not be detected by passive surveillance which occurs through health facilities. Reactive case detection (RACD), or active case finding among households and neighbours of passively identified index cases, is a strategy to address this challenge. With the goal of RACD being the identification and treatment of asymptomatic or other infections that would not otherwise present through the passive surveillance system, it is considered a key malaria strategy for gathering surveillance information [1] and may reduce transmission and facilitate the achievement of malaria elimination [2, 3]. RACD is widely implemented [4], yet it is operationally challenging requiring significant human resources, commodities, and time for an "on-call" team to conduct screenings in villages, often traveling long distances to reach remote locations. There are also limitations with the standard diagnostics used, microscopy or rapid diagnostic test (RDT), to detect low-density infections. Highly sensitive diagnostics are available but the costs and cost-effectiveness of using them is unclear. Further, the costs of conducting RACD in general have not been systematically documented [5, 6].
The detection limit of microscopy or RDTs is typically 100 parasites/µL, and in low endemic settings, a high proportion of asymptomatic infections fall below this threshold [7, 8]. Outside of use in research settings, more sensitive detection methods such as polymerase chain reaction (PCR) are impractical due to high cost, sophisticated training, resources required, and long turnaround time (several hours). Another molecular method called loop-mediated isothermal amplification (LAMP) provides the sensitivity of PCR with fewer requirements. Testing is not point-of-care and requires use of a laboratory, but the assay is simple, does not require sophisticated equipment, and can be performed in half a day to one full day [9, 10]. However, the costs and cost effectiveness of using LAMP in RACD are not clear.
To enable national malaria programmes to assess the feasibility of implementing RACD in their low burden setting, this study aimed to: (1) estimate the cost of implementing RACD using data from the malaria-eliminating district of Aceh Besar, Indonesia; and (2) compare the cost and cost-effectiveness of using a standard diagnostic (microscopy) to more sensitive LAMP for identifying infections during RACD. This information can help guide strategic and budgetary planning for local malaria control programmes, and also help to inform the research, development, and implementation of highly sensitive diagnostics for malaria.
Study design
The study was a prospective economic analysis of costs and cost-effectiveness. The main cost measures were cost per RACD event, per person screened, per population at risk (PAR; defined as total population in each sub-district), and per infection found. The main cost-effectiveness measure was incremental cost-effectiveness ratio (ICER), expressed as cost per malaria infection detected by LAMP versus microscopy.
Study location
Aceh Besar District is located in the western part of Aceh Province on Sumatra Island, Indonesia. Malaria transmission occurs year-round with the higher transmission occurring from January to July. In the past, Plasmodium falciparum and Plasmodium vivax were reported as the main malaria species, but Plasmodium knowlesi has also been reported from the area in 2016 [11]. Due to intensified efforts in case management, vector control, and surveillance, Aceh Besar District has successfully reduced annual malaria incidence from 2.6 cases per 1000 population in 2006 to 0.2 per 1000 in 2014 (population in 2014 was 371,412 [12]). It is one of 114 low endemic districts categorized by the Indonesian government as 'eliminating', with a goal to interrupt transmission by 2020 [13, 14]. As part of the malaria elimination strategy, the District Health Office in 2010 initiated RACD, which is locally referred to as 'contact survey'. After a microscopy-confirmed malaria case is diagnosed at the health facility, designated surveillance staff visit the village of the index case to perform malaria testing among household members and neighbours. Based on WHO and national guidelines, RACD is performed using microscopy and all subjects residing within 500 m of the index case are targeted.
Study population
Index cases were enrolled from four sub-district level health facility sites that reported 78% of all reported cases in Aceh Besar in 2013: Indrapuri, Kuta Cot Glie, Lhoong, and Saree. An additional health facility Lhoknga was also included purposively due to high case burden prior to 2013. RACD was conducted in the villages where index cases resided, and the people reached during RACD were enrolled for this study. The study was conducted over a period of 20 months from May 2014 to December 2015.
Health facility and field procedures
All subjects presenting to health facilities with suspected malaria were assessed for malaria infection by microscopy of blood smears. Microscopy confirmed cases, also referred to as an index case, had a subsequent venous blood draw to generate a dried blood spot (DBS) for LAMP and PCR. Within one to 7 days of the index case report, RACD was conducted among individuals residing in households located within 500 m of the index cases. During an RACD event, blood was collected from individuals by finger prick to prepare slide blood smears and DBS. The RACD team consisted of five people: a microscopist and surveillance officer from the health facility, two community health workers from the village (a midwife plus a village malaria worker or village leader), and the study field coordinator. Up to two return visits were conducted to include any missing residents. The coverage goal of RACD in each of the target area was to recruit a minimum of 40 subjects or at least 80% of the residents within each of the closest five households. Additional details of index case enrolment and RACD have been previously described [11].
Laboratory testing
The microscopists collected blood smears in the field and transported them in closed slide boxes for subsequent examination at the health facility. Slides were fixed and stained with 3% Giemsa. A slide was determined malaria positive if at least one clear form of any malaria parasite species was found after examination of the whole spread of the thick smear. Parasite densities were measured by counting the number of asexual parasites per 200 or 500 white blood cells (WBC) and calculating parasites/µL assuming a WBC count of 8000 parasites/µL in the thick smear. If positive, an additional 100 high-powered fields in the thin smear were examined to determine species [15]. Cross-check of the malaria positive slides for species identifications were done by the district level microscopist. A provincial expert level-certified microscopist did quality assurance (QA) for all positive slides, 10% of randomly selected negatives and to resolve any discrepancies in results between the clinic and district-level microscopists [13].
All DBS samples collected were dried overnight then stored in sealed plastic bags with desiccant. Extraction of DNA and LAMP testing on all samples were performed at the Aceh Provincial Health Laboratory. DNA was extracted from DBS using the Saponin/Chelex-100 method [16]. Using 15 µL of chelex-extracted DNA solution, Pan-LAMP testing followed by Pf-LAMP specific testing for Pan-LAMP positive samples was performed using a commercial Loopamp detection kit [17, 18] in accordance to manufacturer's instructions (Eiken Chemical, Japan) (Limit of detection (LOD) between 1 and 5 parasites/µL). As previously detailed, using DNA chelex-extracted from a second DBS, Pan-LAMP positive and 10% of Pan-LAMP negative samples underwent further molecular testing for QA at the Eijkman Institute for Molecular Biology using nested PCR methods (LOD between 0.1 and 1 parasites/µL) targeting the cytochrome b gene followed by AluI enzyme digestion for species identification and 18S rDNA nested PCR, with positive samples undergoing further P. knowlesi-specific PCR testing [11].
Costing data collection
Costs were collected for RACD programme set-up, training, coordination, and all activities beginning from when an index case was reported from a health facility (e.g. preparing supplies and contacting the index case household) through to sample processing, analysis, and quality assurance conducted after the RACD event. Time spent by personnel on microscopy or LAMP, including the quality assurance by subsequent microscopy and PCR, respectively, was allocated to diagnostic-specific costs as appropriate. Follow-up costs including a return visit to provide treatment to subjects that were initially microscopy-negative but subsequently found to be LAMP-positive were not included.
Data on costs were collected by a local field study coordinator through review of expenditure records. All costs were converted from the local currency to US dollars (USD) using the average mid-year exchange rate for 2015 (1 USD = 13,432 Indonesian Rupiah, from Oanda.com). These data were inputted to a costing tool developed in Microsoft Excel 2010. Costs were organized by location at which the expenses occur (health facility, provincial laboratory, and national laboratory); the type of diagnostic test used (microscopy or LAMP); and the month in which the cost was incurred. Each cost input was grouped into one of five major categories.
Personnel costs covered project staff salaries for trainings, coordination, field activities and laboratory work. Project staff included one full time field coordinator, a part time field team in each of the five sub-districts including one surveillance officer and a microscopist, three part-time laboratory technicians at the provincial and national levels, and one laboratory technician at the national level. Most of the personnel had duties outside the scope of this study, and only supported RACD as index cases presented to health facilities. Thus, specific time contributions of all personnel involved in the RACD activities were logged and later used for approximating the cost of human resources. Time required for initial diagnosis of index cases at health facilities was not included.
Costs associated with any trainings conducted for this study were captured and include costs for training supplies, room rental, and participant per diems.
The cost of services included utilities such as internet, communication, courier services, and vehicle rental/fuel for sample transportation used in conducting RACD. Services utilized prior to the study period but for project setup were included.
Capital costs were initial investments to set up RACD and included the cost of owned motor vehicles used for travel and transportation; electronic devices such as computers, computer accessories, printers, tablets, refrigerators; and laboratory equipment such as microscopes, centrifuges, heat blocks, and PCR machines. If the capital was used for activities other than RACD, a time use percentage was assigned. The cost of capital was valued for the study duration (20 months) after accounting for depreciation based on the useful life years of each capital, and discounted using a rate of 3%. The remaining values of capital at the end of the study period were subtracted. The cost of office space and furniture were not included due to limitations in data availability.
Consumables included field and laboratory supplies such as slides, lancets, alcohol swabs, plastic bags, filter paper, LAMP kits, laboratory reagents, centrifuge tubes, etc. Per unit costs of these consumables were multiplied by the amounts utilized during the study period to estimate the total cost of consumables.
The main outcome measure was number of infections detected by LAMP versus microscopy in RACD. Other measures included number of RACD events and number of individuals screened per RACD event.
To estimate the costs associated with microscopy versus LAMP, RACD costs were separated into 'general RACD costs' and 'diagnostic-specific costs'. General RACD costs covered routine activities related to RACD such as the field visit, including time for preparation, travel, and screening households. Diagnostic specific costs for microscopy and LAMP were calculated by isolating any personnel, training, consumables, processing time, services from general RACD costs. As a key activity for an elimination surveillance programme, particularly for programmes considering the use of highly sensitive diagnostics, QA was included for both microscopy- and LAMP-specific costs [1]. Trainings for microscopy and microscopy QA were conducted in conjunction with the surveillance trainings and included in the general RACD training costs. Cost proportions for each input category were compared for microscopy-specific, LAMP-specific and general RACD costs.
Cost per RACD event and cost per individual screened were calculated by dividing the total cost of conducting RACD using microscopy and/or LAMP during the study period by the total number of RACD events and screened individuals. Cost per population at risk (PAR; defined as total population in each sub-district) was calculated at the sub-district level. Cost per PAR per year was calculated by dividing the total cost of RACD using both diagnostics by the population and by the number of months the study was conducted (20 months). The resulting montly cost per PAR, was then multiplied by 12 (months in a year) to determine the cost per PAR per year. Costs per infection identified were calculated as cost of RACD using microscopy and/or LAMP, divided by the number of infections detected by microscopy and/or LAMP, respectively. The total cost for the study period and annual recurrent programmatic cost of the RACD programme were also calculated. The annual recurrent programmatic cost was approximated by excluding any capital non-recurrent costs from the total cost.
To compare the cost-effectiveness of the different diagnostic methods, the incremental cost-effectiveness ratio (ICER), defined by the difference in cost between two interventions divided by the difference in their effect, was estimated by comparing the cost and outcomes associated with LAMP and microscopy. As general RACD costs were applied to both methods, the differences in costs were due to diagnostic-specific costs and respective yield.
To explore how costs might vary across sites with different index case burdens or prevalence of infection in RACD [19], cost measures were compared across the sub-districts. The cost drivers of RACD across the study sites were also assessed. To consider how changes or differences in diagnostic sensitivity or prevalence of infection in RACD might affect findings, the costs and ICER for different scenarios was estimated based on the costs and outcomes observed in this study.
Enrollment and outcome measures
Study enrollment and laboratory reports have previously been reported [11], but are shown in Fig. 1 for reference. In brief, a total of 36 eligible positive index cases were identified in the health facilities triggering 36 RACD events. Of the 1638 eligible individuals residing in the screening radius of the index cases, 1495 (91%) were enrolled in the study. On average, about 42 individuals were screened or tested per RACD event. Of these individuals tested during RACD, a total of eight additional infections were identified. Three of these additional cases were initially found to be microscopy positive, but one was determined to be a false positive as confirmed by LAMP. An additional five individuals, originally found to be microscopy negative, were positive when tested by LAMP. Thus, seven additional infections found via RACD were confirmed LAMP positives. When the seven LAMP positives underwent PCR for quality assurance, one was negative. In total, six PCR-confirmed cases were identified, with three each from Saree and Lhoong study sites, and were classified as three P. vivax, two P. falciparum, and one P. knowlesi. The remaining three sites (Kuta Cot Glie, Indrapuri, and Lhoknga) identified no additional infections as a result of RACD. A summary of the outcome measures (number of RACD events, subjects screened, and infections identified) for the overall study and by sub-district is shown in Table 1.
Overall cost of RACD using microscopy and LAMP
The total cost of conducting RACD using microscopy and LAMP during the study period was $42,418 (Table 1). On average, the cost per RACD event was estimated to be $1178 and the cost per individual screened was $28. The average cost per infection identified was $7070. As a public health intervention, the annual cost per PAR was estimated at $0.42 averaged across the sub-districts.
Cost and cost-effectiveness by microscopy versus LAMP
Microscopy-specific costs, which consists of consumables, such as slides and Giemsa, personnel time used to process and read the slides, microscopes, and staff training, was calculated at $929 in total, which translated to $0.62 per individual screened (Table 2). LAMP-specific costs, which includes LAMP-specific capital and consumables (kits, DBS, reagents, and laboratory equipment for QA) as well as trainings and personnel time to process and run the blood samples for LAMP with quality assurance, totaled $24,557 over the course of the study. This is equivalent to $16 per individual screened. Consumables, followed by training and personnel costs were the main cost drivers for LAMP (Fig. 2). Compared to a box of 100 microscopy slides, which were purchased for $4.50 (equivalent to $0.05 per test), Pan-LAMP tests cost $3.75 each and Pf-LAMP tests cost $11.97 each. Reagents used for PCR for LAMP QA also constitute to a major share of consumables. General RACD costs, which could not be attributed to either diagnostic specifically, totaled $16,931, or $11 per individual screened. Table 2 also presents costs for overall RACD costs with microscopy and LAMP, RACD with microscopy only, and RACD with LAMP only over the course of the study period, as well as annualized recurrent costs for RACD, microscopy, and LAMP specific costs. The annual recurrent costs, or costs which exclude one-time purchase capital costs, are indicative of the costs that the programme can expect for each year that the intervention is implemented. For example, a programme that has all the necessary capital equipment for LAMP, such as a heat block and PCR machine, can expect to budget $9 per person screened by LAMP, in addition to the annual recurrent cost of RACD.
Cost shares by input category were compared between the diagnostic methods (LAMP and microscopy), as well as to general RACD costs (Fig. 2). Personnel costs accounted for the major share for general RACD and microscopy specific costs, at 41 and 51%, respectively. Consumables accounted for the largest share of LAMP specific costs at 51%, and second largest share for microscopy at 44%. Training cost was the second largest as a share of cost for LAMP and general RACD at 20% each. Four trainings were held between September 2013 and January 2015. Of the four, one training was LAMP-specific laboratory training. The remaining three focused on general RACD protocols, and included refreshers on blood collection techniques for microscopy and LAMP. Personnel time and training were also the main cost drivers for RACD across each study site.
The share of capital costs for LAMP-specific and general RACD activities was at 13% each. A more detailed breakdown of all capital costs can be found in the annex (Additional file 1: Figure S1). Of all capital costs, 61% was from laboratory equipment mainly for LAMP and LAMP QA followed by tablets and accessories (33%). Eight of the ten highest capital costs, ranging from $82 to $1542, were attributed to LAMP or LAMP QA and included laboratory equipment such as a heat block, Gel doc system, a thermomixer, a UV sterilization cabinet, a refrigerator, a centrifuge, and a PCR machine, though all of these items except the heat block and pipette were only used for RACD between 15 and 75% of the time. Usage of the gel doc system, thermomixer, UV Sterilization cabinet, and PCR machines are not crucial for LAMP detection itself, but are important for LAMP QA and represent a large share of the capital cost. Two of the top ten high value capital were attributed to general RACD costs and included seven tablets used for data collection and study laptops. The remaining capital items used for RACD had attributed costs ranging from $1.75 to $74. Additional file 1: Tables S1, S2 provide a more detailed breakdown of input costs by location and cost category.
Two infections were identified among all individuals tested with microscopy. The resulting cost per additional infection identified by RACD using microscopy was estimated to be $8930, where the microscopy-specific cost accounted for only about 5% (or $465 per infection). Six infections were identified via LAMP through RACD at a cost of $6915 each (LAMP-specific cost of $4093 per infection). The ICER of detecting an infection through LAMP compared to microscopy was estimated to be $5907 per infection.
Costs by sub-district
Of the five cost categories, LAMP-specific consumables were the largest cost driver at 34% of the total expense for all sub-districts. Personnel and trainings accounted for the next largest shares of the expense at an average of 27 and 20%, respectively. Capital and services accounted for an average of 13 and 7%, respectively, across the sub-districts. As Lhoknga had no index cases, no services or consumables costs were incurred, which resulted in a larger proportional share of training and capital costs (57 and 37%, respectively).
The distribution of total costs for RACD using microscopy and LAMP varied across the study sites (Table 1). In Lhoong and Saree, which had the highest number of RACD events and individuals screened, the total cost was the highest of the five study sites at $12,703 and $12,748 respectively, and the cost per individual screened was between $25 and $24 per person screened each. With eight RACD events in Kuta Cot Glie, total cost was lower than Saree and Lhoong, with cost per individual screened being similar ($26). With two RACD events, Indrapuri had the highest cost per individual screened at $55. Lhoknga had no RACD events and thus no cost per individual screened, but the site maintained a cost of $4391, primarily due to personnel (including training) and a small amount of capital requirements to be prepared to launch RACD if needed. The cost per PAR per year by sub-district ranged from $0.11 in Lhoknga to $.79 in Lhoong, and averaged $0.42 across the total population of the five sub-districts (Table 1).
Effect of infection prevalence on costs and cost-effectiveness
For settings with lower or higher prevalence of infection compared to Aceh Besar, the costs using LAMP or another equivalent test with 3:1 diagnostic yield relative to microscopy were estimated (Fig. 3, solid line). At 0.4% prevalence of infection, the cost per infection identified is $7070, and declines to $1767 when the prevalence is 1.6%. Cost declines begin to plateau thereafter. The impact of prevalence of infection on ICER was also estimated (Fig. 3, dotted line). As the calculation for ICER is based on cost per infection, ICER also declines with increasing prevalence of infection. At 0.4% prevalence of infection, ICER was $5907, and declines to $1477 when the prevalence of infection is 1.6%. The ICER decline slows and begins to plateau thereafter.
Effect of diagnostic yield on costs and cost-effectiveness
Although LAMP detected threefold more infections than microscopy, our sample size was small. Other diagnostics, existing or in development, may provide a different yield relative to microscopy [20]. Assuming prevalence of microscopy-detectable infection to be 0.13% and base costs similar to LAMP, the impact of diagnostic yield on costs per infection identified and ICER was estimated (Fig. 4). When the yield is three fold relative to microscopy, the cost per infection identified is $7070 (as in our study). When the yield increases to fivefold, the costs decreases to $4242, with the curve nearing a plateau when the yield reaches tenfold, where costs are $2121 per infection identified. The ICER follows the same trend. At a yield of three fold relative to microscopy, the ICER is $5907 and it continues to reduce to $2954 when the yield is fivefold and $1313 when the yield is tenfold relative to microscopy. The same trends would apply to a situation with a higher proportion of low-density infection (e.g. as malaria transmission declines).
RACD is a strategy widely implemented to gather surveillance information in low transmission settings and it may contribute to reductions or interruption of transmission. However, the costs of doing RACD have not been well evaluated. This study investigated the cost of conducting RACD and the cost-effectiveness of different diagnostic methods in identifying additional malaria infections. During the study period of 20 months, 1495 individuals were screened in 36 RACD events yielding six additional cases by microscopy or LAMP, at an estimated total cost of $42,418. The average cost of conducting RACD using microscopy and LAMP was $1178 per event, with the main cost driver being personnel. The average cost of RACD for each individual was $11 for general costs, with an additional $0.62 and $16 per person for microscopy and LAMP, respectively. As a public health intervention, RACD using both diagnostics cost an average of $0.42 per PAR per year. LAMP was more costly but more cost-effective for the detection of infections mainly due to higher diagnostic sensitivity. For RACD using microscopy only, the cost per infection found was $8930 compared to $6915 for RACD using LAMP only. The ICER for RACD using LAMP versus microscopy was $5907 per additional malaria infection detected. As malaria programmes consider active case detection and the integration of highly sensitive diagnostics, these findings may inform strategic and budgetary planning.
Due to the intensified interventions required, it is well-established that malaria elimination compared to control is more costly but that longer term benefits make the pursuit worthwhile [21, 22]. A systematic review on the costs and cost-effectiveness of control interventions by White et al. [23] found the median cost of preventative interventions (insecticide-treated bed nets, indoor residual spraying, intermittent preventative treatment) was $0.60–$6.70 per person and the median costs for case management services (diagnosis, treatment) ranged from $4.32–$30.26 per patient, with the most expensive service being treatment of severe malaria. Our finding that RACD with microscopy and/or LAMP cost $12–$28 per individual screened is consistent with previous reports on the higher cost for elimination versus control interventions. The high cost of $7070 per infection identified also raises the issue of the value of RACD as a low yield activity where case detection rates are generally less than 2% even with highly sensitive diagnostics [24]. However, the value of an intervention should be considered in a broader context. As a public health intervention, the annual cost of RACD using both diagnostics was low, at an average of $0.42 per PAR at the sub-district level.
Despite the high costs, RACD using LAMP versus microscopy led to a lower cost per infection identified (23%) and the ICER of $5907 per additional infection detected favors the use of LAMP or a LAMP-equivalent assay in RACD. Based on our analyses of cost inputs, there would opportunities to mitigate costs. Personnel and LAMP-specific consumables, and not capital, training, or services, accounted for the highest cost shares [25]. Personnel costs could be minimized by better integrating staff in the health system. LAMP-specific consumable costs could be decreased if prices were negotiated or subsidized, or a less expensive highly sensitive diagnostic could be used. In addition, the higher sensitivity of LAMP made it possible to detect P. knowlesi in the study area for the first time. This important benefit may outweigh the high costs of RACD using LAMP.
To explore how costs might vary across sites with different index case burdens or prevalence of infection in RACD, cost measures were compared across the sub-districts. In sub-districts with more RACD events (such as Saree and Lhoong) overall costs were higher than in sub-districts with fewer cases, and consequently the cost per individual screened was lower. Despite having zero cases during the study period, Lhoknga still needed to maintain costs for training "on-call" local health facility personnel as well as capital in the event an index case were to present and RACD would need to be conducted.
To further inform how costs and cost-effectiveness might vary with differences in prevalence of infection or the sensitivity of the diagnostic used, estimated projections show how costs per infection identified along with ICER decrease with increases in prevalence of infection and yield of a diagnostic to detect infections, relative to microscopy (Figs. 3 and 4). As seen in the Fig. 3, the curve began to plateau when the test positive rate or prevalence of infection in RACD increased above 1.6% suggesting that the highest relative cost-savings will be realized in low transmission settings. The curve also began to plateau when the yield of the diagnostic test exceed fivefold–tenfold relative to microscopy, suggesting diminishing returns with use of more sensitive diagnostics [26] when the prevalence is already low. As more sensitive diagnostics are being developed or come to market, these considerations can help to inform decision-making on investments and strategic planning.
There were some limitations of this study. Estimation of the personnel costs relied on self-reported time allocations. Further, due to the few cases in this low transmission setting, limitations exist for the generalizability of the study and precision of the ICER estimate. Extrapolations to consider the influence of prevalence of infection and diagnostic yield were performed, but assumed other fixed factors (epidemiological, or cost-related). In real world implementation, several relevant factors could change and affect costs. For example, cost-effectiveness of LAMP could be improved with discounted prices for LAMP or other less costly diagnostics (e.g. a new highly sensitive histidine-rich protein 2-based rapid diagnostic test [27] could be useful in P. falciparum predominant settings and has lower costs due to a discounted price and does not require laboratory work nor travel back to the households to inform on results). In a more remote and underserved setting, there may be higher costs associated with establishing laboratory infrastructure to conduct LAMP. A new diagnostic may have higher costs than those required for LAMP. These scenarios would increase costs per infection identified and reduce cost-effectiveness. Also, the estimations assume very low parasite densities and do not take into account that in other settings, due to endemicity or species (e.g. P. falciparum presents with higher parasite densities than P. vivax), parasite densities may be different and thus impact the sensitivities and yield of microscopy and LAMP. More empiric data from other settings along with use of more sophisticated modeling techniques could improve generalizability. Additionally, while microscopy and LAMP both require time to acquire results, processing time for LAMP may be longer resulting in a delay in treatment and therefore transmission-blocking, which were not taken into consideration in this analysis. Finally, this study only assessed costs from service provider's perspective, including cost sharing and in-kind donations, and costs are specific to this situation. In other contexts, absolute costs may be different. Future studies can build upon these findings to quantify costs and benefits of conducting RACD by including the broader costs to society when additional infections are not detected and may result in further transmission.
This study had several strengths. Firstly, a detailed and prospective collection of RACD costs was carried out. Retrospective data collection can introduce bias and limit the granularity of the costing data. Importantly, this study fills a critical gap on the economics of focal screen and treat. Previous studies have documented a framework for evaluating the costs of RACD [25], conducted cost analyses of mass screen and treat [28], or identified potentials for operational efficiencies [29], but only one other study has measured the actual costs and that study was from a higher transmission setting where the RACD test positivity rate was 19% [25]. To the best of the authors' knowledge, this study is the first on RACD or focal screening and treatment to report costs from a low transmission setting, costs using a highly sensitive diagnostic, and cost-effectiveness of using a highly sensitive versus standard diagnostic in active case detection.
In summary, in the low transmission setting of Aceh Besar, RACD costs per individual screened were found to be high, though costs per PAR were low. Compared to microscopy, the use of LAMP in RACD was more costly but more cost-effective for the detection of infections, with diminishing returns observed when findings were extrapolated to scenarios with higher prevalence, or using more sensitive diagnostics when prevalence is very low. These findings can inform strategic and budgetary decisions faced by the many countries that are pursuing malaria elimination and considering active case detection with new diagnostics [1, 30, 31].
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Wu L, van den Hoogen LL, Slater H, Walker PG, Ghani AC, Drakeley CJ, et al. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature. 2015;528:S86–93.
Hsiang MS, Greenhouse B, Rosenthal PJ, et al. Reply to Goyal et al. J Infect Dis. 2015;211:1687.
Britton S, Cheng Q, McCarthy JS. Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings. Malar J. 2016;15:88.
Herdiana H, Cotter C, Coutrier FN, Zarlinda I, Zelman BW, Tirta YK, et al. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum. Malar J. 2016;15:468.
Monthly malaria report and findings: January–December 2014–2015. Aceh Besar, Aceh Province, Indonesia: Aceh Besar District Health Office (DHO); 2015.
National malaria control program strategic plan 2015–2019. Indonesia: Ministry of Health Republic of Indonesia; 2014.
Ekawati LL, Herdiana H, Sumiwi ME, Barussanah C, Ainun C, Sabri S, et al. A comprehensive assessment of the malaria microscopy system of Aceh, Indonesia, in preparation for malaria elimination. Malar J. 2015;14:240.
WHO. Basic malaria microscopy. Part 1: learner's guide. Geneva: World Health Organization; 2010.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995;52:565–8.
Aydin-Schmidt B, Xu W, Gonzalez IJ, Polley SD, Bell D, Shakely D, et al. Loop-mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias. PLoS ONE. 2014;9:e103905.
Hopkins H, Gonzalez IJ, Polley SD, Angutoko P, Ategeka J, Asiimwe C. Highly sensitive detection of malaria parasitemia in a malaria-endemic setting: performance of a new loop-mediated isothermal amplification kit in a remote clinic in Uganda. J Infect Dis. 2013;208:645–52.
Muriuki D, Hahn S, Hexom B, Allan R. Cross-sectional survey of malaria prevalence in tsunami-affected districts of Aceh Province, Indonesia. Int J Emerg Med. 2012;5:11.
Daily J. Malaria diagnostics technology and market landscape. 3rd ed. Geneva: UNITAID; 2016.
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van Eijk AM, Ramanathapuram L, Sutton PL, Kanagaraj D, Sri Lakshmi Priya G, Ravishankaran S, et al. What is the value of reactive case detection in malaria control? A case-study in India and a systematic review. Malar J. 2016;15:67.
Larson BA, Ngoma T, Silumbe K, Rutagwera M-RI, Hamainza B, Winters AM, et al. A framework for evaluating the costs of malaria elimination interventions: an application to reactive case detection in Southern Province of Zambia, 2014. Malar J. 2016;15:408.
Imwong M, Hanchana S, Malleret B, Renia L, Day NP, Dondorp A, et al. High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. J Clin Microbiol. 2014;52:3303–9.
Das S, Jang IK, Barney B, Peck Rek JC, Arinaitwe E, et al. Performance of a high-sensitivity rapid diagnostic test for Plasmodium falciparum malaria in asymptomatic individuals from Uganda and Myanmar and naïve human challenge infections. Am J Trop Med Hyg. 2017;97:1540–50.
Silumbe K, Yukich JO, Hamainza B, Bennett A, Earle D, Kamuliwo M, et al. Costs and cost-effectiveness of a large-scale mass testing and treatment intervention for malaria in Southern Province, Zambia. Malar J. 2015;14:211.
Searle KM, Hamapumbu H, Lubinda J, Shields TM, Pinchoff J, Kobayashi T, et al. Evaluation of the operational challenges in implementing reactive screen-and-treat and implications of reactive case detection strategies for malaria elimination in a region of low transmission in southern Zambia. Malar J. 2016;15:412.
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Authors' contributions
MSH, RB, and BZ conceived the paper and prepared the manuscript. BZ coordinated inputs to the draft. RB and BZ conceived the design and conducted the analysis. FC and CC contributed to study design. FC managed sample analysis. FC and IZ managed the local data collection. All authors read and approved the final manuscript.
The authors extend their gratitude to the Indonesian Sub-directorate for Malaria, particularly Dr. Maria Endang and Dr. Ferdinand Laihad, for their contributions.
Competing interests
The authors declare that they have no competing interests.
Availability of data and materials
Data used for this manuscript is available upon request.
Consent for publication
All authors have read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable.
Funding for this work comes from a Grant from the Bill & Melinda Gates Foundation [A121292]. Funding was also provided by National Institute of Allergy and Infectious Diseases at the National Institutes of Health [AI101012 to M.S.H.] and the Horchow Family Fund at the University of Texas, Southwestern [5300375400 to M.S.H.]. The funders had no role in the design or writing of this paper or the decision to submit the paper for publication. The authors were not paid to write this manuscript.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Additional file
Additional file 1: Figure S1.
Cost proportion breakdown of capital costs. Table S1. Detailed summary of input costs (USD) by location. Table S2. Detailed summary of input costs (USD) by cost category. Table S3. Detailed list of top ten capital costs, discounted annually at 3% from year of purchase (USD).
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
About this article
Cite this article
Zelman, B.W., Baral, R., Zarlinda, I. et al. Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia. Malar J 17, 220 (2018). https://doi.org/10.1186/s12936-018-2361-y
DOI: https://doi.org/10.1186/s12936-018-2361-y
- Reactive Case Detection (RACD)
- Loop-mediated Isothermal Amplification (LAMP)
- Incremental Cost-effectiveness Ratio (ICER)
- Test Positivity Rate
- Main Cost Drivers


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subset: commoncrawl


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If you turn the news on the television… its all bad. Fires… murders… wars… hate… bigotry… and the newspaper headlines are the same. Are there ANY good things happening in this world today. Does mankind even care about each other anymore?
Yes. They do… and it was proven to me over the last few weeks.
If you follow me on FaceBook… or Twitter… or here on this blog, you have probably seen me mention "Jerry's Journey" a time or two within the past couple of weeks. Here's what I actually know about the situation…
Jerry was a Viet Nam Veteran. He and his wife had custody of their granddaughter, Brittany. Sadly, his wife passed back in December leaving just him and Brittany to carry on. Jerry paid for his wife's services and ordered a double headstone to be put on the grave and was making payments to cover the cost. And then he was diagnosed with a terminal disease… with just mere weeks left to go.
Many of us have things we would like to do during our lifetimes… a "bucket list" as they are known. Parachuting… white water rafting… climbing Mount Everest… visiting Rome… each bucket list is as different as the person making it. And Jerry had a bucket list, too… but his was simple. And short. Like his time left…
First and foremost… Jerry wanted to ensure Brittany's needs would be met. This would require legal work and was the biggest concern on Jerry's mind.
Secondly… Jerry wanted to get the headstone placed on his wife's, and soon to be his, graves so that he could place flowers for her at least once.
Next… as a Viet Nam Veteran, Jerry wanted to visit The Wall in Washington DC. This was no small task considering that he was in Alabama… his health was perilous… and his time quickly running short.
Lastly… Jerry wanted to go with peace of mind. He was worried about his final expenses and wanted to ensure they were covered so his beloved Brittany wouldn't be left with the burden of a final bill.
So although his bucket list was short, only four items, to Jerry and Brittany it was seemingly unattainable.
But then you came along.
A friend posted an item on FaceBook that became known as "Jerry's Journey." The four items were listed. You asked how you could help… where you could send a few dollars to help with the short list.
The first item on the list was quickly solved. The legal papers to ensure a safe, loving environment were executed and the largest concern Jerry had was put to rest. Brittany's care was taken care of.
Next… you stepped up to provide for Jerry to visit "his boys" at The Wall. A trip was quickly planned and prayers that he would have the strength to make it there and back were said. The trip was conducted within days of the need being known. The picture accompanying this post is of Jerry as he slowly made his way from one end of The Wall to the other… stopping to rest his hand on each panel… to touch his boys one last time.
As requests to help came in, an account was established to help defray the cost of the headstone. And you didn't take long. Just before departing to Washington DC, enough funds were received to cover the cost and installation of the stone. A call to the company, with an explanation of the short time frame involved, led them to rush the order. The headstone was in place when Jerry returned from his trip. Tired and weak, he still summoned the strength to visit his wife's grave to place a bouquet of flowers.
This left just one item on his bucket list… his final expenses. He couldn't expect more from strangers than they had already given. People he didn't know… and would never have the opportunity to meet… coming through to help someone in their time of need. This final item weighed heavily on Jerry's mind.
So once again, a plea for funds was posted about Jerry's Journey. You had helped already, but would you… could you… help just a little more? Would you help Jerry spend what surely were his last few days without this one last burden? It was a lot to ask for someone you'd never know.
Jerry's earthly journey ended this past Thursday… surrounded by those he loved… and as much at peace as we could make his last days. You allowed his time to be spent peacefully without worrying over minor items. He spent it with Brittany and those that he loved. And you showed him that, regardless of what is said in the news, the kindness of strangers… does still exist.
John Bunyan is quoted as saying "You have not lived until you have done something for someone who can never repay you."
So you stranger… you that gave and helped Jerry pass peacefully… you have now lived.
And that's MY take…


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TGIF, friends!!
Okay, so I know ramen noodles aren't exactly healthy, but they're cheap, quick and easy to make, and my kids LOVE them! Todd and I don't mind them either, but they can be a little bland so I decided to add in some leftover flank steak that we had from the night before along with some veggies I had in the fridge. Well holy moly, y'all...it was SO good!!! I didn't measure anything so I'm just going to guesstimate some things, but just know that you can't really mess this up!
3 packs of beef flavor ramen
Medium rare grilled flank steak
3 cups of beef broth
2 cups of water
1 small bag of baby carrots sliced
1 cartoon of fresh mushrooms
1 medium size yellow onion
2tsp of butter
5tsp of low sodium soy sauce or coconut aminos
Salt and pepper to taste
Use a large pot and boil the 3 packs of ramen noodles as directed on package, but use half water and half beef broth instead of water only. Put all three beef flavor seasonings in as well.
While the noodles are boiling in a separate pan add two tablespoons of butter and toss in your sliced carrots, mushrooms, and onions and sautéed until soft.
Then add your steak into the sautéed vegetables along with 5tsp of coconut aminos and let it simmer for 5 to 10 minutes.
Last, add your steak and vegetables into the ramen, bring to boil, then reduce heat and let simmer for 10 to 20 minutes.
** If you prefer egg in your ramen for extra protein and flavor, this is the soft boil egg recipe I used when I made this recipe again earlier this week.
This picture makes me smile...as a kid I LOVED watermelon!! And while the pre-sliced watermelon in the store is pretty good, nothing beats a watermelon fresh from the garden. Our three kiddos ate this entire thing in four days, and yes, I said all three because Reese was able to eat some in her baby fruit feeder.
If you are a fan of banana pudding then you MUST make this recipe asap!! It's been a few years since I had made this one, and oh my goodness, it was amazing!! Once you make this, I am willing to bet you'll never make the regular kind again :)
My sweet water baby! All of our babies have always liked the water, but I'm pretty sure Reese was a fish in another life because this baby LOVES it!
I had a few questions about my swimsuit and Reese's hat so I'm linking everything up below.
My Stripe Swimsuit (only $23) // Wrap Cover-up // Reeses swim hat // Similar Baby Swimsuit
Last, but not least, I have to brag on these two for a second! They have both been so amazing not only with us having a new baby, and quarantine, but with each other as well. And Carsons new favorite sport is fishing, so just for her brother she pretends to love it as well :)


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How to Claim the Recoverable Depreciation
Most of what you or your business own depreciates with time. Computers become obsolete, office furniture suffers wear and tear, inventory becomes outdated and machinery breaks down. As a result, they're all worth less than when you bought them. When you file an insurance claim, your insurer will take the depreciation into account when cutting you a check. However, you should be able to file a second claim for recoverable depreciation.
Actual Costs and Replacement
Property insurance comes in two main flavors, covering either actual costs or replacement costs. The difference is significant. Say you have an actual-cost policy and part of your roof tears off in a storm. Actual-cost coverage pays for the replacement price of your roof, less depreciation. If your roof repairs would cost $5,000 but the roof has $3,000 of depreciation, you get $2,000, less any deductible. You'll have to find the remaining $3,000 in your pocket.
Replacement coverage pays enough for you to repair or buy replacements for what you lost, up to the coverage limits of the policy. If you need $5,000 in roof repairs, the insurance will pay that much, less your deductible.
Some insurance shoppers wonder which coverage is required by law. Legally, you can go either way and decide not to get property insurance at all. If you take out a mortgage to buy a home or a warehouse, however, your lender will probably insist on you taking out insurance as well.
Dealing With Insurance Depreciation
If you lose new property that's suffered little depreciation, the insurer can probably cut you one check to cover your losses. If depreciation is in play, and you have replacement coverage, you'll need two checks.
Say you work from home on your laptop. Someone breaks in and steals it. The insurer looks at the model and the software you installed on it and concludes it would take $1,600 to buy a comparable replacement computer. Unfortunately, your laptop was three-years-old and depreciation is $200 a year, so you get a check for only $1,000, or less if a deductible applies.
Since you paid for replacement cost coverage, that's not the end of the story. You get to go out, buy a replacement computer and submit the receipt to the insurer. The company then cuts you a check for the $600 of recoverable depreciation.
You need your receipts because the insurance company will only reimburse you for what you spend. If you find a bargain model that's only $1,400, they'll cover $400 for depreciation. If your parents buy you a new laptop as a gift, or you decide not to buy one, you don't get a second check. If you buy a $2,000 laptop, you won't get more than the $600 in recoverable depreciation. Anything above that is on you. Regardless of how much you spend, you still get to keep the first check.
The Clock Is Ticking
Another limitation on recovering depreciation is that the insurer won't wait forever. You have to start on the repairs or purchasing within a certain time frame, or you won't be able to claim the second check. Travelers' Insurance, for example, says that you should notify them within 180 days that you intend to make a recoverable depreciation claim. Other insurers will have their own rules.
Keep Good Records
Just telling your insurer you've made the repairs, then asking for the second check, isn't going to cut it. Document everything you do and everything you pay. Save your invoices, contracts, receipts and canceled checks, make copies and submit them to your insurer. Make it clear what the paperwork covers: the repairs you paid for and the replacement items you bought. Include your claim number to make it easier for the insurer to process the paperwork speedily.


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My father captured my energy by creating my "be still" spot
and that began the harnessing of my delightfully chaotic energy.
My preschool years landed me on an island with an armload of friends living in the rest home next door. They had happy face wrinkles and white hair. On the other side lived my grandparents. In front of our home was a lake where we swam and fished and skated. So, my early schooling was wise elders and natural science. I was a child of busyness with the energy that has propelled me throughout my lifetime, back then it was enjoyed as Dennis the Menace—only I and my sister were girls.
My grandmother was schooled in child development in the early 1900's and she was filled with lovely childhood ideas. My mother crafted and created opportunity for imagination, read to us daily and directed us in the proper ways to talk, walk and eat. She shared us with her community activities of church and scouts. There was always abundance of paper and crayons and scissors and glue. She did not fear big messes. My father was a carpenter. If he could dream and invent it he could build it, and if it was broken he fixed it. If we broke it we fixed it with him—we seldom bought new.
"You see that Red Wing Blackbird?
How would you like him to be your friend?"
"I can't."
He admonished, "Can't won't be in this family's vocabulary.
Where there is a will there is a way.
Anything is possible when you learn to do it with help."
And he whispered, "Let's learn to be still."
How to create a "Be Still" learning spot
- Pick a "Be Still" spot for yourself where you can go and learn to notice the unnoticeable. This is your place to learn to calm and grow yourself. First simply go to observe then bring a journal or sketch pad.
- Share your "Be Still' spot with your child. Learn to watch the little together. Learn to ask questions. Have quiet fun.
- Ask your child, "What's your favorite place in the yard/neighborhood/around here?" Let your child choose their place—it may be under a special tree, by the downspout, in a garden, a swing, on top of a slide. Walk with your child to their favorite nearby place. It must be outdoors where they can sit and watch and learn. Ask your child, "What do you like about this special place?" "How does it make you feel?" Hopefully, it is a calming place, if not you will need to create one together. "Let's make this your special 'Be Still' place and you can share stories with me of everything you learn here." Provide a small box that is water proof and won't blow away with paper and drawing tools for doodles, sketches, and musings that the child can take to the "Be Still" spot.
Needless to say a great big will rose up inside of me. To empty my busy brain in meditation only created more energy—to focus on creation opened and soothed my mind and filled it with brilliance.
I couldn't sit still and everytime I moved Blackie.
Tiny step by tiny step my father challenged each of my weaknesses to become strengths. He often said, "Show me. Tell me. Ask me." "I don't know, let's find out," from my father meant we were going on a book adventure. A big set of child encyclopedias, next to the adult bigger books held the answers to my unanswerable questions. I learned to trust my father's ways of learning and value my thoughts and curiosity.
Blackie became my first own real animal friend and in time together we learned many things. He had a special call for "more" of whatever I was feeding him and he even ate out of my hand. I saw Blackie leave in fall and come back in spring after the ice crystals on the lake sang to me as a choir before sinking into open water. And I learned to calm myself and be still while setting aside my robust energy. Blackie didn't forget me when he returned north. He still expected me to feed him sunflower seeds and corn. I guessed he missed me.
Meanwhile I had begun working on befriending a chipmunk "Chippie" and a squirrel "Peanuts" but that's another story.
Blackie died the summer I was four. Death of a friend was new to me. Millie's big old black cat Midnight pounced and ate him. Dad hugged and held me close and we buried what was left of him in the garden. We talked about how cats eat birds and birds eat bugs. It was the way of the world and sometimes when we reach into another creature's world especially in the outdoors life happens and we need to get over it and be thankful for the gifts of the relationship. Blackie gave me so much more life value than I gave him—he taught me to sit still and learn to calm myself to notice. At least for a while.
In my personal sit spot, I learned about life and myself as long as I remained observant with my full being. As long as I sat with quiet respect for my surroundings and the creature who arrived to meet me. I met frogs and toads carefully seeing how they differed. I watched as spiders wove webs between tall stalks of grass to catch flies. I noticed that the ants carried huge items compared to their small size. I saw angle worms left upon the earth after the rain. I saw fish jump, dragon flies connect and muskrats swim. I watched patterns of life and followed ripples of water and wafts of air. And each thing I saw or smelled or heard birthed questions that my older friends were happy to answer or help me discover where to find an answer or how to figure it out.
How I use the sit-spot as an adult.
I use the skills I learned in my dad's "Sit Spot" everyday of my life. It is the skill that has allowed me to see my daughter through her eyes and value her. It is the skill that has allowed me to reach traumatized individuals and animals and pause giving the space for valuing their learning process. It has allowed me to inspire learning in positive small precious steps. More than that it allows me (most times – after all I am human) to keep a balance in the storms of life.
2 No, I keep myself calm and quiet, like a little child on its mother's lap
—I keep myself like a little child. Psalm 131:2 (CJB)
Thank you for letting me share. Feel free to SHARE – like and comment.
All the best


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Kraftwerk have recently played three 3D concerts in Munich which was a small introduction to their 3D video Installation exhibition in the Kunstbau at the Lenbachhaus in Munich. Kraftwerk's programmed world of images and sounds, an immersive total work of art, will for the first time be experienced outside the concert hall. A multi-channel 3D video installation specially developed for the Kunstbau will make for a worthy presentation of Kraftwerk's unique and influential position within the history of the fine and the performing arts. The exhibition will be opened from October,15 till November 13, 2011.
Kraftwerk@ Lenbachhaus
Images source: Kraftwerk@ Lenbachhaus


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Tourist attractions in Chłopy and its neighbourhood
Our cabins at the seaside is the perfect tourist offer for enthusiasts of active leisure. Picturesque landscapes and walking paths, cycle routes, broad and clean beaches are only some of the numerous assets of Chłopy. Beautiful scenery and the appeal of Chłopy will allow you to relax at the Polish seaside. In comparison to other resorts by the Baltic Sea, Chłopy is not a very crowded resort and offers a peaceful, relaxing atmosphere.
It is a perfect place for holidays with children or friends, as well as a romantic stay for two.
First historical records come from the 18th century century, when the village was called Borowo. Since 1840 it is known by the name Chłopy (German: Bauerhufen). At that time it was already advertised as a popular bathing resort. Chłopy is located in the central part of the Polish coast, right by the coastline, 6 km to the west of Mielno, the most popular resort in the area (especially among young people).
The village itself is rather small, with about 200 permanent residents. Chłopy is the only preserved fishing village in Poland. It comprises a couple of 19th-century wattle and daub cottages. It is particularly interesting that these cottages face the road with their gable walls. The whole village was entered into the register of monuments because of its well-preserved traditional layout.


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DuPont, WA, 98327
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Pediatric Services
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Your Childs First Visit
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Meet the Team
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Tracy Takenaka, DDS
Meet the Team
Office Tour
For Parents
Why Choose a Pediatric Dentist?
Your Childs First Visit
Patient Forms
Financial & Office Policies
Patient Testimonials
Pediatric Services
Sedation Dentistry
Child Dental Care FAQs
DuPont, WA
Q. Why should my child see a pediatric dentist instead of our regular family dentist?
Pediatric dentistry
is a dental specialty that focuses on the oral health of young people. Following dental school, a pediatric dentist receives two to three years of additional specialty training in the unique needs of infants, children, and adolescents, including those with special health needs.
Q. At what age should my child have their first dental visit?
A. "First visit by 1st birthday" is the general rule. To prevent dental problems, your child should see a pediatric dentist when the first tooth appears – usually between 6 and 12 months of age – and certainly no later than his/her 1st birthday.
Q. How should I clean my baby's teeth?
A. A toothbrush with soft bristles and a small head, especially one designed for infants, is the best choice for babies. Brushing at least once a day, at bedtime, will remove plaque bacteria that can lead to decay.
Q. What is baby bottle tooth decay, and how can I prevent it?
A. Baby bottle tooth decay is a pattern of rapid decay associated with prolonged nursing. It happens when a child goes to sleep while breast-feeding and/or bottle-feeding. During sleep, the flow of saliva is reduced, and the natural self-cleansing action of the mouth is diminished. Avoid nursing children to sleep or putting anything other than water in their bedtime bottle.
Q. How can I help my child through the teething stage?
A. When teeth erupt, sore gums are part of the normal eruption process. The discomfort is eased for some children by use of a teething biscuit, a piece of toast or a frozen teething ring. Your pharmacy should also have medications that can be rubbed on the gums to alleviate the discomfort.
Q. Can thumb sucking be harmful for my child's teeth?
A. Thumb and pacifier sucking habits that go on for a long period of time can create crowded, crooked teeth or bite problems. If children are still sucking their thumbs or fingers when their permanent teeth erupt, a mouth or
space appliance
may be recommended by your pediatric dentist. Most children stop these habits on their own.
Q. When should my child start using toothpaste?
A. Current guidelines from the American Dental Association and American Academy of Pediatric Dentistry recommend using a smear or grain of rice sized amount of fluoridated toothpaste for children 6 months to 3 years of age and a small pea sized amount for children 3 to 6 years of age. Fluoride toothpaste should not be used on children less than 6 months old.
Q. If my child gets a toothache, what should I do?
A. To comfort your child, rinse his/her mouth with warm salt water, and apply a cold compress or ice wrapped in a cloth on your child's face if it is swollen. Do not put heat or aspirin on the sore area, but you may give the child acetaminophen for pain. Please see us as soon as possible.
Q. My child plays sports. How should I protect my child's teeth?
should be a top priority on your child's list of sports equipment. Athletic mouth protectors, or mouthguards, are made of soft plastic and fit comfortably to the shape of the upper teeth. They protect a child's teeth, lips, cheeks, and gums from sports-related injuries. Any mouthguard works better than no mouthguard, but a custom-fitted mouthguard fitted by our dentist is your child's best protection against sports-related injuries.
Q. If my child gets a cavity in a baby tooth, should it still be filled?
A. Primary, or "baby," teeth are important for many reasons. Not only do they help children speak clearly and chew naturally, but they also aid in forming a path that the permanent teeth can follow when they are ready to erupt. Some of them are necessary until a child is 12 years old or older. Pain, infection of the gums and jaws, impairment of general health, and premature loss of teeth are just a few of the problems that can happen when baby teeth are neglected. Also, because tooth decay is really an infection and will spread, decay on baby teeth can cause decay on permanent teeth. Proper care of baby teeth is instrumental in enhancing the health of your child.
Q. What should I do if my child knocks out a permanent tooth?
A. First of all, remain calm. If possible, find the tooth and hold it by the crown (top) rather than the root. Replace the tooth in the socket, and hold it there with clean gauze or a washcloth. If you can't put the tooth back in the socket, place the tooth in a clean container with milk or water, and take your child and the glass immediately to the
Pediatric Dentist
. Time is essential, so the faster you act, the better your chances of saving the tooth.
Call Children's Dentistry of DuPont at
(253) 244-9778
for more information.
Request an Appointment
Map/ Directions
Patient Forms
Office Hours:
Mon: 8am - 5pm (Clinic hours by special arrangement)
Tues: 8am - 5pm
Wed: 8am - 5pm
Thu: 8am - 5pm
Limited Fri: 8am - 1pm by special arrangement
(253) 244-9778
1200 Station Drive Suite 180
DuPont, WA 98327
Copyright © 2018-2022
Children's Dentistry of DuPont
WEO Media (Touchpoint Communications LLC)
. All rights reserved.
Pediatric Dental Care FAQs • Children's Dentistry of DuPont, WA
Are you curious about your child's dental care needs? At Children's Dentistry of DuPont, we have the answers to your questions. Click on the link to view our FAQ page about child dental care.
Children's Dentistry of DuPont, 1200 Station Drive, Suite 180 DuPont, WA 98327 \ (253) 244-9778 \ childrensdentistryofdupont.com \ 9/15/2022 \ Page Phrases: pediatric dentist DuPont WA \


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wikiHow is a "wiki," similar to Wikipedia, which means that many of our articles are co-written by multiple authors. To create this article, volunteer authors worked to edit and improve it over time.
This article has been viewed 3,864 times.
National Chocolate Day is celebrated every year on October 28th. It is a fun holiday that is completely dedicated to, you guessed it, chocolate. If you love eating chocolate a lot, and you want to know how you can celebrate National Chocolate Day and have a great time doing it, then simply move on to step one below.
1Go to the store and purchase chocolate. Even if it's not your normal day to shop, don't be afraid to go to the store and by some! You are celebrating National Chocolate day, after all. You can buy any chocolate item or items that you want, along with any type of chocolate.
2Research about chocolate. There are so many different types, and so many interesting facts, so if you research, you're bound to learn something new about chocolate.
3Bring chocolate to work with you. If you get a break, then you can eat it during that time, or on your lunch break. Whichever time is easier for you.
- If you have children, and you allow them to have it, pack some chocolate in their lunches if you pack one for them. In the morning, you can tell them that it's national chocolate day, so you packed them a nice treat.
- If you cannot eat the chocolate during the day, then make sure that the chocolate doesn't melt, and save it for when you get home.
4Tell other people that it's National Chocolate Day. Some people may know, some may not know. Some may be shocked, some may not care. You won't know what their reaction will be unless you tell them.
5Wear brown clothing if you have any. Although it may not be fashionable, you can tell people it's for National Chocolate Day.
- Alternatively, if you don't have any brown clothing, you can wear white and/or black to represent either white chocolate or cookies and creme flavored chocolate. You can also wear either white and/or black, or brown. The choice is yours.
6Give chocolate to your co workers, or family members. Even if they don't like chocolate, they will most likely appreciate your gift, because it's the thought that counts.
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There are many different kinds and forms of chocolate out there, so feel free to eat and give out whichever chocolate you would like to.Thanks!
If you decide to give your kids chocolate in their school lunch, if you are making them one, put in the type of chocolate that you know they like best. This will make them even more excited when they see the surprise in their lunch box.Thanks!
- Do not give chocolate to someone you know is allergic, or someone you know can't have chocolate for medical reasons. If you do not know if they can or not, then ask them before you give it to them. This will help you be sure whether they can eat it or not.Thanks!
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MILWAUKEE RECREATION PLANS 10TH ANNUAL FAMILY FUN AT HALLOWEEN GLEN Event combines Halloween fun with outdoor education This year marks the 10th Anniversary of Milwaukee Recreation's "natural alternative" to the usual haunted houses. Family Fun at Halloween Glen enables youth to learn about nature through a fun and interactive program in the outdoor setting of Hawthorn Glen, Milwaukee Recreation's 23-acre nature center at 1130 N. 60th St. The program will run every half hour beginning at 6:00, 6:30, 7:00, and 7:30 p.m. on Friday, October 17 and Saturday, October 18 (rain or shine). "Families who attend Halloween Glen should expect a fun, Halloween-themed experience with an educational twist," says MPS Assistant Recreation Supervisor Kevin Reed. "We've hired actors to dress up as trick-or-treaters, skeletons, and other Halloween characters, but they won't be scaring anyone. Instead, this talented group will present interactive skits at seven elaborately decorated stations along the lighted trails of Hawthorn Glen. For example, our skeleton will talk about how dead things decompose." Following the program, families will make their own Halloween art (a new addition to the event) and enjoy refreshments like pretzel bones, halloweenies, and witches' brew. Families with children between the ages of 4 and 12 will enjoy the program most, but everyone is welcome to attend for $4.00 per person (children 3 and under may attend for free). Participants must register in advance by calling 475-8180 or downloading the registration form at www.MilwaukeeRecreation.net. Because parking is limited at Hawthorn Glen, all participants must park at MPS Central Services, 5225 W. Vliet St., and use the free shuttle service to and from the event. Milwaukee Recreation is a non-profit department of Milwaukee Public Schools, established in 1911 to provide the entire community with affordable and enriching recreational activities. For more information about Milwaukee Recreation, visit www.MilwaukeeRecreation.net or contact Brian Hoffer at (414) 475-8938. ### Brian M. Hoffer Milwaukee Public Schools Division of Recreation and Community Services 5225 W. Vliet St., Room 163 Milwaukee, WI 53208 T 414.475.8938 F 414.475.8541 http://www.MilwaukeeRecreation.net Milwaukee Recreation — Experience Life
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Ralph Bunche Becomes First African American to Win Nobel Peace Prize
In 1950 the Norwegian Nobel Committee awarded the Nobel Peace Prize to the first non-white person, the African-American and United Nations (UN) official Ralph Bunche.
He received the Peace Prize for his efforts as mediator between Arabs and Jews in the Israeli-Arab war in 1948-1949. These efforts resulted in armistice agreements between the new state of Israel and four of its Arab neighbours: Egypt, Jordan, Lebanon and Syria.
Two members of the Norwegian parliament nominated Ralph Bunche for the Nobel Peace Prize. Both had connections to the newly founded United Nations. One was Norway's first UN ambassador, and the other was a member of the Norwegian UN delegation. The nomination stated: "Although it can not be said to be Dr. Bunche's merit, but the development process itself that made the parties end the hostilities, there can be no doubt that it is Dr. Bunche's merit that the challenging negotiations over a ceasefire were brought to a positive result in a relatively short time".
The nominators had several motives. Awarding the Nobel Peace Prize to Bunche "would thereby not only honour him personally, but express trust and faith in the ability of the United Nations to solve international disputes by way of mediation between the parties". Furthermore, the nominators could not "neglect to mention that giving the Nobel Peace Prize to a member of the coloured race is a boost to peace in itself". Thus the Peace Prize was meant to strengthen the UN and to serve as an initiative against racism as well as to honour Ralph Bunche.
The Nobel Peace Prize is an international award given yearly since 1901 for achievements in peace. The prize, which includes about $1.3 million, a gold medal, and a diploma, is presented on December 10, the anniversary of the death of Alfred Nobel, its founder. Dr. Ralph J. Bunche was the first African American to win the Nobel Peace Prize, in 1950. Fourteen years later, Dr. Martin Luther King Jr. was the second, the youngest person thus far to receive the Peace Prize. As Peace Laureates, they are on a list of organizations and people that includes Theodore Roosevelt, 1906; Woodrow Wilson, 1910; Mother Teresa, 1979; Desmond Tutu, 1987; Nelson Mandela, 1993; and Jimmie Carter, 2002. Certainly the life of Dr. Bunche demonstrates that no African American of the 20th century, however prominent, escaped the racial forces shaping the United States, forces that led to the Civil Rights Movement of the 1960s.


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Veep At Paleyfest 2014! Julia Louis-Dreyfus! Tony Hale! Reid Scott! Timothy Simons! Autographs! And More!
March 28, 2014 Fanboying!, Paleyfest
Tonight was the final Paleyfest of 2014 for me. Technically, it's the penultimate evening for the annual television series events of q and a's that bring together the casts of shows with a reunion or two. Share on Facebook


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Challenge of Protecting Mass Gatherings in a Post-9/11 World: Hearing Before the Committee on Homeland Security, House of Representatives, One Hundred Tenth Congress, Second Session, July 9, 2008 [open pdf - 300KB]
From the opening statement of Bennie G. Thompson: "When Americans think of mass gathering events, the Super Bowl, the national conventions and the Pope's recent visit come to mind. How the Department of Homeland Security manages and coordinates these high-profile national security events is certainly worthy of discussion, but that is a discussion for another day. Today, we will turn our attention to the challenges of securing mass gatherings that are not considered national special security events, that do not have the Federal Government coming in to run security and are held in communities that do not have huge amounts of resources for security. Think of State fairs, collegiate sporting events and even large shopping complexes during the holiday season. Mass gatherings, whether they have national security event rating or not, could be particularly tempting targets for Al Qaeda and other terrorist organizations with the goal of killing or injuring the most people, destroying the most infrastructure and having the greatest impact possible with the least amount of effort." Statements, letters, and materials submitted for the record include those of the following: Bennie G. Thompson, Sheila Jackson Lee, Robert B. Stephan, Roger T. Rufe Jr., Thomas H. Blackwell, Scott McCartney, Douglas Reynolds.
|Report Number:
Serial No. 110-124
Public Domain
|Retrieved From:
Government Printing Office, Congressional Hearings: http://www.gpoaccess.gov/chearings/index.html
|Media Type:


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Star Wars Battlefront II (EZA New Republic Alliance)
I'm new to the forums but A long time EZA fan and new Patron looking to find some people who know some things about love and respect to play video games with. . . . . . I'm also a HUGE Star Wars fan (insert touching childhood story about first action figure/movie/game).
If any Allies are looking for people to play battlefront 1(2015) or Battlefront II(2017) Let's start an "Easy Alliance". I play Battlefront 1 on PC, and will be switching to Ps4 for battlefront II.
Love and Respect!
PS username: FN-1991
jifw52 last edited by
Yes! I'm a huge Star Wars fan, and I love Battlefront! It's such a jolly game! I'm so hyped for its sequel!
PSN: jifw52
Love & Respect.
Billy last edited by
If/when I get Battlefront 2, I would totally love to have some folks to play with. I'm on PSN: BluebeardBill. One caveat, though: I'm pretty awful at online multiplayer shooters, so I may need to ride your coattails to victory.
Churchy last edited by
I'm already playing Battlefront on PS4, and I will be getting Battlefront 2 as there's a group who are getting it as well.
PSN: Churchy1310
Awesome! I play Battlefront on PS4 but my level is much lower than the PC version. Lets play sometime. I'll add you guys. See you on the battlefield!
@Billy It's all good. No skill level required, just a ps4 and a controller.
SabotageTheTruth last edited by
Has Galactic Conquest been confirmed or denied for this release? It's honestly the main reason I used to play Battlefront back in the day so.. I probably won't be hopping in without it.
The idea of having a galactic conquest mode with teams would be extremely impressive.. but I'm trying not to get my hopes up too much.
@SabotageTheTruth No confirmation yet, although no details have really been revealed other than there will be a single player campaign and multiplayer. Probably more news at EA play.
Anyone wanna group up and play this Saturday?
jifw52 last edited by
@savey_studentii Sounds like hype! Are you in the ps4 EZA Community? Perhaps we could get others to join us via there
I think I am, but I'm not sure cause isn't there an official one and a fan created one. I'll check again this evening.
It would be SUPER FUN to play with some allies!
Hey Allies,
Does this Saturday (tomorrow) at like 1:00pm central (11 pacific?) time work?
Lotias Global Moderator last edited by
Glad to see a little group seem to be gathering up to play together! EZA friendship for the win! I might actually buy this on release. I wasnt a huge fan of the first game. However, the more I see of the sequel the more I want to play it. I can't believe they didn't bring in content from all the films in the first game. To be fair it felt like there was a huge lack of content all in all in the first game. This time around though with the campaign and all I feel like I should be game


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So Soiled Mattress & The Springs is playing at LA everything store Family at 7pm tonight but between the three members of the band, the dudes from Teenage Teardrops, the employees of the store and the random Canter's denizens, there will only be room for three or four more people inside. But go there anyway because hanging is fun and amps make things easy to hear from far away. You can also elbow (gently) up front to get your copy of Soiled saxplayer Matthew Thurber's new comic 1-800-MICE signed and maybe kissed with gold lipstick. That's Thurber's illustration for an old SM&S 12" above in case you're wondering what you're in for. Go here for tonight's flyer and also the rest of the band's West Coast dates.
LA: Soiled Matt
May 31, 2007


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What's on our mind? You can read about it in our blog. Whether it's ideas from the industry or emerging trends, you can read about it here. And once in a while, we may throw in a book review or some other surprise. So keep checking in. We're glad to have you reading along.
Account View Access with Wealth Vision Reports
Excited to release a new and updated website that will give you access to view your LPL accounts and networked accounts. Including access to consolidated reporting with Wealth Vision.Read More
What Is the Value of Your Business?
In the third quarter of 2017, more than 2,500 small businesses were sold. The median sale price was $225,000, up from $200,000 the year before.¹ As a business owner, ascertaining the value of your business is important for a...Read More


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Investor Testimonials
What Investors Think About Berg Capital
Rob Nicoski, CFA, CPA
Portfolio Manager at Disciplined Growth Investors
Let me start by first saying that over the course of my nearly two decade career as an institutional money manager literally hundreds of sales professionals have "called on me." I say "called on me" because that has generally been the extent of their effort. Few have taken the time to fully understand exactly what I am looking for as a long-term fundamental investor, and fewer yet have been able to add meaningful value once they have developed that level of discernment. Josh is one of those few. Not only has he committed the time to develop a clear understanding of our investment philosophy and process, he is an independent thinker that does not let the constraints of a limited product set stifle his willingness to think creatively about how he can add real value to our process. Finally, years in the trenches have taught me that life is too short to partner with individuals that lack integrity, no matter how bright and motivated they might be. To that end, I have been given the opportunity to get to know Josh over the past several years. He is a good man; one that I believe would never compromise his integrity or take advantage of a client to earn a buck.
Matt Arens, CEO
Senior Portfolio Manager at First Light Asset Management
I can say without reservation that Josh ranks near the top of the list of salespeople that I have worked with over the last 15 years. He is passionate about finding and presenting great investment ideas. He is a great partner and has earned the loyalty of many analysts and portfolio managers.
Josh Pesses
Portfolio Manager, Goodwood Capital Management
Josh initially serviced my firm during his time as an institutional sales rep at Leerink Swann. Josh demonstrated a unique value proposition. He went above and beyond to bring us actionable, non-consensus recommendations. His deep understanding of potential investments and his collaborative spirit gave us a tremendous head start on our own diligence. I continue to work with Josh at Berg Capital Markets. His ability to identify value very early on and connect companies seeking a quality base of investors make him partcularly well-suited for the role. Most importantly, Josh is extremely ethical and diligent - qualities of utmost importance for any partnership.
Jack Thrift
Jack Thrift, CPA
I worked with Josh early in his career as an institutional sales person at Pacific Growth Equities. Over the years working together, he rose to prominence as one of our more capable and seasoned professionals and ended up managing some of our largest accounts. His clients trust his judgement and ability to help them add alpha in their portfolios.
Casey Ryan
Senior Analyst, Lyon Street Capital
Josh Berg is an outstanding professional. Josh is focused and driven while maintaining the vision to work towards high level strategic goals. In my experience Josh has outworked and outsmarted his competition and has been a leader in all his organizations from a production stand point and as a leader in the organization. I have had the pleasure to know Josh personally for 10 years and have worked with him at two employers, both where he drove excellent results for each organization.
Rob Wilson
Institutional Portfolio Analyst at MFS Investment Management
Josh has been a valuable resource to me in my role as a Senior Investment Analyst supporting three funds with total assets under management of $8 billion. His understanding of corporate strategy and financial analysis and unique insight into all aspects of the healthcare industry enabled me to take quick, yet thoughtful action on several large equity positions. Furthermore, I found working with Josh both efficient and enjoyable, thanks to his honest and straight-forward style of communication.
Andrew Rich
Principal and Portfolio Manager at MindShare Capital Management
Josh has covered me for several years and provided numerous profitable ideas. He is extremely dedicated and I highly recommend Josh. He vets his analysts' work thoroughly and provides his own color in many instances. He has a good grasp on the market and what moves stocks. Josh has a good personality and has been a pleasure to work with.
Christopher Thomson
Equity Analyst at MindShare Capital Management
As a buy-side analyst, Josh's contributions as a sell-side institutional equity salesman have been essential to my job duties and knowledge base. I relied on Josh to augment my understanding of the healthcare and medical device space. His expertise, attention to detail and work ethic have proven to be significantly better than the vast majority of his peers.
Phil Fisher
PM at Temagami Capital
I was privileged to work with Josh for three years and have maintained a strong on-going relationship with him since we worked together. He is a highly energetic, focused and entrepreneurial individual. He has a very positive work attitude and follows projects through from beginning to end without need for oversight. He demands the best of himself and that is reflected in the high quality of his work. Josh is a self-starter who strives to make a difference and for his work to have an impact. I consider it an honor to have worked with him.
The contents of this website: (i) do not constitute an offer of securities or a solicitation of an offer to buy securities, and (ii) may not be relied upon in making an investment decision related to any investment offering by Berg Capital Markets, LLC, or any affiliate, or partner thereof ("Berg"). Investment offerings and investment decisions may only be made on the basis of a confidential private placement memorandum issued by Berg Capital Markets, LLC, or one of its partner/issuers. Berg Capital Markets, LLC does not warrant the accuracy or completeness of the information contained herein.