Impact of a spatial repellent intervention on Anopheles kdr insecticide resistance allele in Sumba, Indonesia.

BACKGROUND: The emergence of insecticide resistance and outdoor transmission in malaria-endemic areas underlines the urgent need to develop innovative tools, such as spatial repellents (SR), that may circumvent this residual transmission. With limited options for effective insecticides, regular resistance monitoring is warranted for selecting and using appropriate tools. This study evaluates the pyrethroid knockdown resistance (kdr) allele before and after implementing a transfluthrin-based spatial repellent (SR) intervention in placebo-treated clusters. METHODS: This study looks at the frequency distribution of the kdr allele in Sumba Island from June 2015 to August 2018. Insecticide susceptibility tests were carried out on female Anopheles sp. aged 3-5 days against permethrin 21.5 µg/ml, deltamethrin 12.5 µg/ml, and transfluthrin 10 µg/ml using CDC bottle assay. PCR sequencing of representative samples from adult mosquito collections and insecticide tests revealed the presence of kdr mutations (L1014F and L1014S) in the VGSC gene. RESULTS: A total of 12 Anopheles species, Anopheles tesselatus, Anopheles. aconitus, Anopheles barbirostris, Anopheles kochi, Anopheles annularis, Anopheles maculatus, Anopheles sundaicus, Anopheles flavirostris, Anopheles balabacensis, Anopheles indefinitus, Anopheles subpictus, and Anopheles vagus were analysed. Anopheles vagus and An. sundaicus predominated in the larval populations. Susceptibility assays for all insecticides identified fully susceptible phenotypes in all species examined. Anopheles increasing frequency of kdr mutant alleles during the 3 year SR deployment was observed in both SR-treated and placebo areas, a statistically significant increase occurred in each arm. However, it is unclear how significant SR is in causing the increase in mutant alleles. The L1014S, knockdown resistance east type (kdr-e) allele was detected for the first time among the mosquito samples in this study. The L1014F, knockdown resistance west type (kdr-w) allele and heteroduplex form (wild-type-mutant) were found in almost all Anopheles species examined, including An. vagus, An. aconitus, An. subpictus, An. tesselatus, An. annularis, An. flavirostris and An. sundaicus. CONCLUSION: The presence of fully susceptible phenotypes over time, along with an increase in the frequency distribution of the L1014F/S mutations post-intervention, suggest drivers of resistance external to the study, including pyrethroid use in agriculture and long-lasting insecticidal nets (LLINs). However, this does not negate possible SR impacts that support resistance. More studies that enable the comprehension of possible SR-based drivers of resistance in mosquitoes need to be conducted.

Scientific achievements and reflections after 20 years of vector biology and control research at the Pu Teuy mosquito field research station, Thailand.

Additional vector control tools are needed to supplement current strategies to achieve malaria elimination and control of Aedes-borne diseases in many settings in Thailand and the Greater Mekong Sub-region. Within the next decade, the vector control community, Kasetsart University (KU), and the Ministry of Higher Education, Science, Research and Innovation must take full advantage of these tools that combine different active ingredients with different modes of action. Pu Teuy Mosquito Field Research Station (MFRS), Department of Entomology, Faculty of Agriculture, Kasetsart University (KU), Thailand was established in 2001 and has grown into a leading facility for performing high-quality vector biology and control studies and evaluation of public health insecticides that are operationally relevant. Several onsite mosquito research platforms have been established including experimental huts, a 40-m long semi-field screening enclosure, mosquito insectary, field-laboratory, and living quarters for students and researchers. Field research and assessments ranged from 'basic' investigations on mosquito biology, taxonomy and genetics to more 'applied' studies on responses of mosquitoes to insecticides including repellency, behavioural avoidance and toxicity. In the course of two decades, 51 peer-reviewed articles have been published, and 7 masters and 16 doctoral degrees in Entomology have been awarded to national and international students. Continued support of key national stakeholders will sustain MFRS as a Greater Mekong Subregion centre of excellence and a resource for both insecticide trials and entomological research.

Impact of a spatial repellent product on Anopheles and non-Anopheles mosquitoes in Sumba, Indonesia.

BACKGROUND: The East Nusa Tenggara province, Indonesia, contributed to 5% of malaria cases nationally in 2020, with other mosquito-borne diseases, such as dengue and filariasis also being endemic. Monitoring of spatial and temporal vector species compositions and bionomic traits is an efficient method for generating evidence towards intervention strategy optimization and meeting disease elimination goals. METHODS: The impact of a spatial repellent (SR) on human biting mosquitoes was evaluated as part of a parent cluster-randomized, double-blinded, placebo-controlled trial, in Sumba, East Nusa Tenggara. A 10-month (June 2015-March 2016) baseline study was followed by a 24-month intervention period (April 2016 to April 2018)-where half the clusters were randomly assigned either a passive transfluthrin emanator or a placebo control. RESULTS: Human-landing mosquito catches documented a reduction in landing rates related to the SR. Overall, there was a 16.4% reduction (21% indoors, and 11.3% outdoors) in human biting rates (HBR) for Anopheles. For Aedes, there was a 44.3% HBR reduction indoors and a 35.6% reduction outdoors. This reduction was 38.3% indoors and 39.1% outdoors for Armigeres, and 36.0% indoors and 32.3% outdoors for Culex species. Intervention impacts on the HBRs were not significant and are attributed to large inter-household and inter cluster variation. Anopheles flavirostris, Anopheles balabacensis and Anopheles maculatus individually impacted the overall malaria infections hazard rate with statistically significance. Though there was SR-based protection against malaria for all Anopheles species (except Anopheles sundaicus), only five (Anopheles aconitus, Anopheles kochi, Anopheles tessellatus, An. maculatus and An. sundaicus) demonstrated statistical significance. The SR numerically reduced Anopheles parity rates indoors and outdoors when compared to the placebo. CONCLUSION: Evidence demonstrating that Anopheles vectors bite both indoors and outdoors indicates that currently implemented indoor-based vector control tools may not be sufficient to eliminate malaria. The documented impact of the SR intervention on Aedes, Armigeres and Culex species points to its importance in combatting other vector borne diseases. Studies to determine the impact of spatial repellents on other mosquito-borne diseases is recommended.

Residual Malaria Transmission in Select Countries of Asia-Pacific Region: Old Wine in a New Barrel.

BACKGROUND: Despite substantial reductions in malaria burden and improvement in case management, malaria remains a major public health challenge in the Asia-Pacific region. Residual malaria transmission (RMT) is the fraction of total transmission that persists after achievement of full operational coverage with effective insecticide-treated bed nets (ITNs)/long-lasting insecticidal nets (LLINs) and/or indoor residual spray interventions. There is a critical need to standardize and share best practices for entomological, anthropological, and product development investigative protocols to meet the challenges of RMT and elimination goals. METHODS: A systematic review was conducted to describe when and where RMT is occurring, while specifically targeting ownership and usage of ITN/LLINs, indoor residual spray application, insecticide susceptibility of vectors, and human and vector biting behavior, with a focus on nighttime activities. RESULTS: Sixty-six publications from 1995 to present met the inclusion criteria for closer review. Associations between local vector control coverage and use with behaviors of human and mosquito vectors varied by locality and circumstance. Consequently, the magnitude of RMT is insufficiently studied and analyzed with sparse estimates of individual exposure in communities, insufficient or incomplete observations of ITN/LLIN use, and the local human population movement into and from high-risk areas. CONCLUSIONS: This review identified significant gaps or deficiencies that require urgent attention, namely, developing standardized procedures and methods to estimate risk exposure beyond the peridomestic setting, analytical approaches to measure key human-vector interactions, and seasonal location-specific agricultural or forest use calendars, and establishing the collection of longitudinal human and vector data close in time and location.

Variable residual activity of K-Othrine® PolyZone and Actellic® 300 CS in semi-field and natural conditions in the Democratic Republic of the Congo.

BACKGROUND: Indoor Residual Spray (IRS) against vector mosquitoes is a primary means for combating malaria transmission. To combat increased patterns of resistance to chemicals against mosquito vectors, alternative candidate insecticide formulations should be screened. With mortality as the primary endpoint, the persistence of residual efficacy of a polymer-enhanced pyrethroid suspension concentrate containing deltamethrin (K-Othrine® PolyZone-KOPZ) applied at 25 mg active ingredient (ai)/m2 was compared with a microencapsulated organophosphate suspension formulation of pirimiphos-methyl (Actellic® 300CS-ACS) applied at 1 g ai/m2. METHODS: Following standard spray application, periodic contact bioassays were conducted for at least 38 weeks on four types of wall surfaces (unbaked clay, baked clay, cement, and painted cement) sprayed with either KOPZ or ACS in simulated semi-field conditions. Similarly, two types of existing walls in occupied houses (painted cement and baked clay) were sprayed and examined. A colonized strain of female Anopheles arabiensis mosquitoes were exposed to treated or untreated surfaces (controls) for 30 min. For each wall surface test period, 40 treatment mosquitoes (4 cones × 10) in semi-field and 90 (9 cones × 10) in 'natural' house conditions were used per wall. 30 mosquitoes (3 cones × 10) on a matching unsprayed surface served as the control. Insecticide, wall material, and sprayed location on wall (in houses) were compared by final mortality at 24 h. RESULTS: Insecticide, wall material, and sprayed location on wall surface produced significant difference for mean final mortality over time. In semi-field conditions, KOPZ produced a 72% mean mortality over a 38-week period, while ACS gave 65% (p < 0.001). Painted cement wall performed better than other wall surfaces throughout the study period (73% mean mortality). In the two occupied houses, KOPZ provided a mean mortality of 88%, significantly higher than ACS (p < 0.001). KOPZ provided an effective residual life (≥ 80% mortality) between 7.3 and 14 weeks on experimental walls and between 18.3 and 47.2 weeks in houses, while ACS persisted between 3 and 7.6 weeks under semi-field conditions and between 7.1 and 17.3 weeks in houses. Household painted cement walls provided a longer effective residual activity compared to baked clay for both formulations. Greater mortality was recorded at the top and middle sections of sprayed wall compared to the bottom portion near the floor. CONCLUSION: KOPZ provided longer residual activity on all surfaces compared to ACS. Painted cement walls provided better residual longevity for both insecticides compared to other surfaces. Insecticides also performed better in an occupied house environment compared to semi-field constructed walls. This study illustrates the importance of collecting field-based observations to determine appropriate product active ingredient formulations and timing for recurring IRS cycles.

The Role of the Private Sector in Supporting Malaria Control in Resource Development Settings.

Industrial operations of the private sector, such as extraction, agriculture, and construction, can bring large numbers of people into new settlement areas and cause environmental change that promotes the transmission of vector-borne diseases. Industry-related workers and communities unduly exposed to infection risk typically lack the knowledge and means to protect themselves. However, there is a strong business rationale for protecting local resident employees through integrated vector control programs, as well as an ethical responsibility to care for these individuals and the affected communities. We discuss the role and challenges of the private sector in developing malaria control programs, which can include extensive collaborations with the public sector that go on to form the basis of national vector control programs or more broadly support local healthcare systems.

Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study.

BACKGROUND: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. METHODS AND FINDINGS: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. CONCLUSIONS: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

Indoor residual spray bio-efficacy and residual activity of a clothianidin-based formulation (SumiShield® 50WG) provides long persistence on various wall surfaces for malaria control in the Democratic Republic of the Congo.

BACKGROUND: Bio-efficacy and residual activity of SumiShield® 50WG (50%, w/w) with active ingredient clothianidin, a neonicotinoid compound, was assessed using an insecticide-susceptible laboratory strain of Anopheles arabiensis. Implications of the findings are examined in the context of potential alternative insecticides for indoor residual spraying in Lualaba Province, Democratic Republic of the Congo. METHODS: Contact surface bioassays were conducted for 48 weeks on four types of walls (unbaked clay, baked clay, cement, painted cement) in simulated semi-field experimental conditions using two different doses of clothianidin active ingredient (200 mg ai/sq m and 300 mg ai/sq m). Additionally, two types of walls (painted cement and baked clay) were examined in occupied houses using the 300-mg dosage. Laboratory-reared An. arabiensis were exposed to treated surfaces or untreated (controls) for 30 min. Mortality was recorded at 24-h intervals for 120 h. RESULTS: Under semi-field experimental conditions, there was no significant difference in mortality over time between the two doses of clothianidin. The mortality rates remained above 60% up to 48 weeks on all four wall surface types. The formulation performed better on cement and unbaked clay with a mean final mortality rate above 90%. Under natural conditions, there was no significant difference in response between baked clay and painted cement walls with a mean final mortality rate above 90%. The insecticide also performed significantly better in natural settings compared to semi-field experimental conditions. CONCLUSION: Depending on the type of experimental surface, the residual activity of the two doses of clothianidin was between 28 and 48 weeks based on a 60% mortality endpoint. Clothianidin at 300 mg ai/sq m applied on two house walls (baked clay or painted cement) performed equally well (> 80% mortality) on both surfaces up to week 41 (approximately 9.5 months). Extended bioassay holding periods (up to 120 h) may present with excess natural mortality in the untreated controls, thus complicating analysis.

Spatial and temporal patterns of dengue incidence in northeastern Thailand 2006-2016.

BACKGROUND: Dengue, a viral disease transmitted by Aedes mosquitoes, is an important public health concern throughout Thailand. Climate variables are potential predictors of dengue transmission. Associations between climate variables and dengue have usually been performed on large-scale first-level national administrative divisions, i.e. provinces. Here we analyze data on a finer spatial resolution in one province, which is often more relevant for effective disease control design. The objective of this study was to investigate the effect of seasonal variations, monthly climate variability, and to identify local clusters of symptomatic disease at the sub-district level based on reported dengue cases. METHODS: Data on dengue cases were retrieved from the national communicable disease surveillance system in Thailand. Between 2006 and 2016, 15,167 cases were recorded in 199 sub-districts of Khon Kaen Province, northeastern Thailand. Descriptive analyses included demographic characteristics and temporal patterns of disease and climate variables. The association between monthly disease incidence and climate variations was analyzed at the sub-district level using Bayesian Poisson spatial regression. A hotspot analysis was used to assess the spatial patterns (clustered/dispersed/random) of dengue incidence. RESULTS: Dengue was predominant in the 5-14 year-old age group (51.1%). However, over time, dengue incidence in the older age groups (> 15 years) gradually increased and was the most affected group in 2013. Dengue outbreaks coincide with the rainy season. In the spatial regression model, maximum temperature was associated with higher incidence. The hotspot analysis showed clustering of cases around the urbanized area of Khon Kaen city and in rural areas in the southwestern portion of the province. CONCLUSIONS: There was an increase in the number of reported dengue cases in older age groups over the study period. Dengue incidence was highly seasonal and positively associated with maximum ambient temperature. However, climatic variables did not explain all the spatial variation of dengue in the province. Further analyses are needed to clarify the detailed effects of urbanization and other potential environmental risk factors. These results provide useful information for ongoing prediction modeling and developing of dengue early warning systems to guide vector control operations.

School-based malaria prevalence: informative systematic surveillance measure to assess epidemiological impact of malaria control interventions in the Democratic Republic of the Congo.

BACKGROUND: In southern Democratic Republic of the Congo, malaria transmission is stable with seasonal fluctuations. Different measurements can be used to monitor disease burden and estimate the performance of control programmes. Repeated school-based malaria prevalence surveys (SMPS) were conducted from 2007 to 2014 to generate up-to-date surveillance data and evaluate the impact of an integrated vector control programme. METHODS: Biannual SMPS used a stratified, randomized and proportional sampling method. Schools were randomly selected from the entire pool of facilities within each Health Area (HA). Subsequently, school-children from 6 to 12 years of age were randomly selected in a proportional manner. Initial point-of-care malaria diagnosis was made using a rapid detection test. A matching stained blood film was later examined by expert microscopy and used in the final analysis. Data was stratified and analysed based on age, survey time and location. RESULTS: The baseline SMPS (pre-control in 2007) prevalence was approximately 77%. From 2009 to 2014, 11,628 school-children were randomly screened. The mean age was 8.7 years with a near equal sex ratio. After exclusion, analysis of 10,493 students showed an overall malaria prevalence ratio of 1.92 in rural compared to urbanized areas. The distribution of Plasmodium falciparum malaria was significantly different between rural and urban HAs and between end of wet season and end of dry season surveys. The combined prevalence of single P. falciparum, Plasmodium malariae and Plasmodium ovale infections were 29.9, 1.8 and 0.3% of those examined, respectively. Only 1.8% were mixed Plasmodium species infections. From all microscopically detected infections (3545 of 10,493 samples examined), P. falciparum represented 88.5%, followed by P. malariae (5.4%) and P. ovale (0.8%). Cases with multiple species represented 5.3% of patent infections. Malaria prevalence was independent of age and gender. Control programme performance contributed to a significant decrease in mean P. falciparum infection density in urban compared to rural locations. Some rural areas remained highly refractory to control measures (insecticide-treated bed nets, periodic indoor residual spraying). CONCLUSION: The SMPS is a useful longitudinal measurement for estimating population malaria prevalence and demonstrating disease burden and impact of control interventions. SMPS can identify refractory areas of transmission and thus prioritize control strategies accordingly.

Phylogenetic Relationships Among Malaria Vectors and Closely Related Species in Thailand Using Multilocus DNA Sequences.

The evolutionary and taxonomic status is important for understanding speciation events and phylogenetic relationships between closely related vector and nonvector species. This information is useful for targeting important disease vector species groups for the development of novel genetic-based vector and pathogen control methods. In this study, different phylogenetic analyses were performed to reconstruct phylogenetic trees for the primary malaria vectors in Thailand based on sequence information of 4 DNA fragments from the nuclear and mitochondrial regions. The primary Anopheles species in the subgenus Cellia involved in malaria transmission in Thailand separate clearly into 3 distinct clades: the Leucosphyrus group, Minimus subgroup, and Maculatus group. The phylogenetic trees based on different reconstructed algorithms and different gene regions provided congruent phylogenetic status of the mosquito species studied. The phylogenetic relationships of malaria vector species examined followed similar patterns based on morphological characters. An estimate of the divergence time among the Anopheles species infers that they were present during the Eocene and Miocene periods (>41 million years ago). Congruent phylogenetic analysis of malaria vectors is presented with different algorithms and gene regions. The nuclear TOLL6 fragment appears useful for molecular phylogenetic, species DNA barcode, and Anopheles population genetic analyses.

Feasibility and implementation of community-based malaria case management with integrated vector control in the Democratic Republic of Congo.

BACKGROUND: Malaria prevalence in the Mulumbu Health Area in Lualaba Province, Democratic Republic of the Congo has remained high (>70 %) despite repeated vector control (indoor residual spray) and mass insecticide-treated bed net coverage. Therefore, a pilot study was implemented to attack the parasite directly and demonstrate the feasibility and acceptability of community case management of malaria (CCMm) using trained community health workers (CHWs). METHODS: A 13 month prospective evaluation of CCMm was undertaken in 14 rural villages. Focus group discussions and structured interviews were conducted in pre- and post-intervention periods to assess community acceptability of CCMm. Weekly data collected by CHWs assessed program impact over time, matched with malaria school-based prevalence surveys (MSPS) in the Mulumbu Health Area (CCMm study arm) compared to a comparison (non-CCMm) arm in the Mpala Health Area approximately 25 km apart. RESULTS: Overall population perception of the CCMm was highly positive. 6619 community contacts were managed by CHWs from which 1433 (21.6 %) were malaria positive by rapid detection tests during the 10 month intervention. Among the malaria infected, 94.7 % (1358) were recorded as 'uncomplicated' infections with 99.7 % provided full course of treatment. CHWs referred 278 (4.2 %) patients deemed 'complicated' to a designated primary health center for advanced care. While pre-intervention MSPS data revealed significantly higher (p = 0.0135) malaria in the CCMm area compared to the non-CCMm area, at post-intervention there was no statistical difference (p = 0.562) between the two areas. Notably, for the first time, no malaria-related deaths were recorded in the 14 CCMm intervention villages during observation. CONCLUSION: Community case management of malaria was shown to be an effective and promising strategy for prompt and effective management of malaria. It was well accepted by the community and showed evidence of a reduction in malaria morbidity and mortality. Further refinement of CCMm implementation, cost implications and sustainability is advised before expanding the programme.

The double burden of disease among mining workers in Papua, Indonesia: at the crossroads between Old and New health paradigms.

BACKGROUND: As the global shift toward non-communicable diseases overlaps with the unfinished agenda of confronting infectious diseases in low- and middle-income countries, epidemiological links across both burdens must be recognized. This study examined the non-communicable disease-infectious disease overlap in the specific comorbidity rates for key diseases in an occupational cohort in Papua, Indonesia. METHODS: Diagnosed cases of ischaemic heart disease, stroke, hypertension, diabetes (types 1 and 2), chronic obstructive pulmonary disease, asthma, cancer, HIV and AIDS, tuberculosis, and malaria were extracted from 22,550 patient records (21,513 men, 1037 women) stored in identical electronic health information systems from two clinic sites in Papua, Indonesia. Data were collected as International Classification of Diseases, 10th Revision, entries from records spanning January-December 2013. A novel application of Circos software was used to visualize the interconnectedness between the disease burdens as overlapping prevalence estimates representing comorbidities. RESULTS: Overall, NCDs represented 38 % of all disease cases, primarily in the form of type 2 diabetes (n = 1440) and hypertension (n = 1398). Malaria cases represented the largest single portion of the disease burden with 5310 recorded cases, followed by type 2 diabetes with 1400 cases. Tuberculosis occurred most frequently alongside malaria (29 %), followed by chronic obstructive pulmonary disease (19 %), asthma (17 %), and stroke (12 %). Hypertension-tuberculosis (4 %), tuberculosis-cancer (4 %), and asthma-tuberculosis (2 %) comorbidities were also observed. CONCLUSIONS: The high prevalence of multimorbidity, preponderance of non-communicable diseases, and extensive interweaving of non-communicable and infectious disease comorbidities highlighted in this cohort of mining workers in Papua, Indonesia reflect the markedly double disease burden increasingly plaguing Indonesia and other similar low- and middle-income countries - a challenge with which their over-stretched, under-resourced health systems are ill-equipped to cope. Integrated, person-centered treatment and control strategies rooted in the primary healthcare sector will be critical to reverse this trend.

Evaluation of a Noncontact, Alternative Mosquito Repellent Assay System.

A novel noncontact repellency assay system (NCRAS) was designed and evaluated as a possible alternative method for testing compounds that repel or inhibit mosquitoes from blood feeding. Deet and Aedes aegypti were used in a controlled laboratory setting. Using 2 study designs, a highly significant difference were seen between deet-treated and untreated skin placed behind the protective screens, indicating that deet was detected and was acting as a deterrence to mosquito landing and probing behavior. However, a 2nd study showed significant differences between protected (behind a metal screen barrier) and unprotected (exposed) deet-treated forearms, indicating the screen mesh might restrict the detection of deet and thus influences landing/biting response. These findings indicate the prototype NCRAS shows good promise but requires further evaluation and possible modification in design and testing protocol to achieve more desirable operational attributes in comparison with direct skin-contact repellency mosquito assays.

Comparison of rapid diagnostic test Plasmotec Malaria-3, microscopy, and quantitative real-time PCR for diagnoses of Plasmodium falciparum and Plasmodium vivax infections in Mimika Regency, Papua, Indonesia.

BACKGROUND: The World Health Organization recommends malaria be diagnosed by standard microscopy or rapid diagnostic test (RDT) before treatment. RDTs have been used with greater frequency in the absence of matching blood slide confirmation in the majority of RDT reported cases in Mimika Regency, Papua Province, Indonesia. Given the importance of RDT in current health system as point-of-care tool, careful validation of RDT product performance for providing accurate malaria diagnosis is critical. METHODS: Plasmotec Malaria-3 (XW-P07) performance was evaluated by comparing it with paired blood film microscopy and quantitative real-time PCR (qPCR). Consecutive whole blood samples were derived from one clinic in Mimika as part of routine passive malaria case detection. RDT results were read by two trained technicians and interpreted by consensus. Expert microscopic examination of blood slides was cross-checked by observer-blinded second reader and a third examiner if discordant between examinations. qPCR was used as the 'gold standard', followed by microscopy for the outcome/disease variable. Comparison analysis included sensitivity (Sn), specificity (Sp), positive and negative predictive values (PPV & NPV), and other diagnostic screening performance measures for detecting Plasmodium falciparum and Plasmodium vivax infections. RESULTS: Overall malaria positive samples from qPCR was 42.2% (175/415 samples); and from matching blood slides 40.5% (168/415) of which those infections with relatively low parasite densities ≤100/µl blood was 5.7% of P. falciparum and 16.5% of P. vivax samples examined. Overall RDT performance when compared with microscopy for detecting P. falciparum was Sn:92%, Sp:96.6%, PPV:88%, NPV:97.8%, Kappa:0.87; and for P. vivax Sn:72.9%, Sp:99.1%, PPV:95.4%, NPV:93.4%, Kappa:0.79. Overall RDT performance when compared with qPCR for detecting P. falciparum was Sn:92%, Sp:96.6%, PPV:88%, NPV:97.8%, Kappa:0.87; and for P. vivax Sn:66%, Sp:99.1%, PPV:95.4%, NPV:90.9%, Kappa:0.73. CONCLUSIONS: Plasmotec Malaria-3 test showed good overall performance scores in precision for detecting P. falciparum, but lower values regarding sensitivity and negative likelihood ratio for detecting P. vivax, a finding partly associated with greater frequency of lower density P. vivax infections compared to P. falciparum in this study. In particular, the negative likelihood ratio (>0.1) for P. vivax detection indicates RDT lacked sufficient discriminating exclusion power falling below general acceptance criteria.

Non-communicable disease risk factor patterns among mining industry workers in Papua, Indonesia: longitudinal findings from the Cardiovascular Outcomes in a Papuan Population and Estimation of Risk (COPPER) Study.

OBJECTIVES: Non-communicable diseases (NCDs) constitute an increasing slice of the global burden of disease, with the South-East Asia region projected to see the highest increase in NCD-related deaths over the next decade. Mining industry employees may be exposed to various factors potentially elevating their NCD risk. This study aimed to assess the distribution and 5-year longitudinal trends of key metabolic NCD risk factors in a cohort of copper-gold mining company workers in Papua, Indonesia. METHODS: Metabolic indicators of NCD risk were assessed among employees (15 580 at baseline, 6496 prospectively) of a large copper-gold mining operation in Papua, Indonesia, using routinely collected 5-year medical surveillance data. The study cohort comprised individuals aged 18-68 years employed for ≥1 year during 2008-2013. Assessed risk factors were based on repeat measures of cholesterol, blood glucose, blood pressure and body weight, using WHO criteria. RESULTS: Metabolic risk indicator rates were markedly high and increased significantly from baseline through 5-year follow-up (p<0.001). Adjusting for gender and age, longer duration of employment (≥10 years) predicted raised cholesterol (adjusted OR (AOR)=1.13, p=0.003), raised blood pressure (AOR=1.16, p=0.009) and overweight/obesity (AOR=1.14, p=0.001) at baseline; and persistent raised cholesterol (AOR=1.26, p=0.003), and both incident (AOR=1.33, p=0.014) and persistent raised blood glucose (AOR=1.62, p=0.044) at 3-year follow-up. CONCLUSIONS: Individuals employed for longer periods in a mining operations setting in Papua, Indonesia, may face elevated NCD risk through various routes. Workplace health promotion interventions and policies targeting modifiable lifestyle patterns and environmental exposures present an important opportunity to reduce such susceptibilities and mitigate associated health risks.

Comparison of Field and Laboratory-Based Tests for Behavioral Response of Aedes aegypti (Diptera: Culicidae) to Repellents.

The repellent and irritant effects of three essential oils-clove, hairy basil, and sweet basil-were compared using an excito-repellency test system against an insecticide-resistant strain of Aedes aegypti (L.) females from Pu Teuy, Kanchanaburi Province. DEET was used as the comparison standard compound. Tests were conducted under field and controlled laboratory conditions. The most marked repellent effect (spatial noncontact assay) among the three test essential oils was exhibited by sweet basil, Ocimum basilicum L. (53.8% escaped mosquitoes in 30-min exposure period) under laboratory conditions while hairy basil, Ocimum americanum L. and clove, Syzygium aromaticum (L.) Merill et. L.M. Perry from laboratory tests and sweet basil from field tests were the least effective as repellents (0-14%). In contrast, the contact assays measuring combined irritancy (excitation) and repellency effects found the best contact irritant response to hairy basil and DEET in field tests, whereas all others in laboratory and field were relatively ineffective in stimulating mosquitoes to move out the test chambers (0-5.5%). All three essential oils demonstrated significant differences in behavioral responses between field and laboratory conditions, whereas there was no significant difference in contact and noncontact assays for DEET between the two test conditions (P > 0.05).

Establishment of Diagnostic Doses of Five Pyrethroids for Monitoring Physiological Resistance in Aedes Albopictus in Thailand.

Monitoring insecticide resistance of Aedes albopictus is required for implementing effective dengue and chikungunya vector control in Thailand. The World Health Organization standard susceptibility test for adult mosquitoes was used to determine the baseline susceptibility of a pyrethroid-susceptible laboratory strain of Ae. albopictus to 5 different pyrethroids (deltamethrin, permethrin, bifenthrin, cypermethrin, and α-cypermethrin). Subsequently, the respective established diagnostic doses (0.026% deltamethrin, 1.024% permethrin, 0.570% bifenthrin, 0.237% cypermethrin, and 0.035% α-cypermethrin) were used to test field-collected Ae. albopictus from Rayong, Koh Chang, and Pong Nom Ron. As expected, the laboratory strain was completely susceptible to all pyrethroid insecticides at the established concentrations. Rayong mosquitoes were found to be highly susceptible to bifenthrin, cypermethrin, and α-cypermethrin. Koh Chang mosquitoes were susceptible to only deltamethrin and permethrin. Pong Nom Ron mosquitoes were resistant to all pyrethroids tested. Routine assessment of these baseline results should guide future resistance monitoring to pyrethroid insecticides in Ae. albopictus in Thailand.

BIONOMICS AND ECOLOGY OF ANOPHELES LITORALIS ON BONGAO ISLAND, TAWI-TAWI PROVINCE, PHILIPPINES: IMPLICATIONS FOR VECTOR CONTROL.

Entomological surveys were conducted to identify Anopheles malaria vector species, their feeding and resting behaviors, and characterization of larval habitats on Bongao Island, Tawi-tawi Province, in July and November, 2007. Survey parameters included all-evening human-landing collections (HLC), evening buffalo-baited trap (BBT) collections, daytime indoor and outdoor adult resting collections, adult female age-grading, identification of natural Plasmodium infections in mosquitoes, larval habitat identification and physical/biological characterization, and adult insecticide susceptibility assays. Both surveys revealed the predominant and putative malaria vector species on Bongao Island is Anopheles litoralis. Anophelesflavirostris was collected on only one occasion. The HLC during the July survey produced approximately 4 mosquitoes/human/night (mhn). The November survey yielded 1.27 mhn due, in part, to inclement weather conditions during time of sampling. Anopheles litoralis host seeking behavior occurred throughout the evening (06:00 PM - 06:00 AM) with peak biting between 10:00 PM and 04:00 AM. This species exhibited stronger zoophilic behavior based on comparison of HLC and BBT data. HLC showed a slightly greater exophagic (outdoor) behavior (1.4:1 ratio). During the July collection, an older adult population was present (75% parous) compared to the lower numbers of An. litoralis dissected in November (25% parous). Albeit a small sample size (n=19), 10.5% of An. litoralis dissected contained midgut oocysts of Plasmodium. Daytime adult resting harborages included biotic and abiotic sites in and around partially shaded, brackish water habitats where immature stages were common. Anopheles litoralis was found susceptible to pirimiphos-methyl and four different synthetic pyrethroids. This survey provides further epidemiological evidence of the importance of An. litoralis in malaria transmission on Bongao Island, and presumably throughout much of the Sulu Archipelago in the southern Philippines. Published observations of this species remain very limited and further investigations on the bionomics and epidemiological importance of this species are needed. Both ecological and human factors in malaria transmission are presented with implications for improved control of An. litoralis and prevention of infection.