Rounds Of Indoor Residual Spraying Research Articles

Impact of population based indoor residual spraying in combination with mass drug administration on malaria incidence and test positivity in a high transmission setting in north eastern Uganda

BackgroundMass drug administration (MDA) and indoor residual spraying (IRS) are potent malaria burden reduction tools. The impact of combining MDA and IRS is not well documented. We evaluated the impact of MDA + IRS compared to IRS alone at a high transmission site in Eastern Uganda.MethodsA quasi-experimental study was implemented in Toroma and Kapujan subcounties in north eastern Uganda. Both subcounties received four rounds of IRS using primiphos-methyl (Acttellic SC300) 6–8 months apart from December 2016 to December 2018. Eligible residents of Kapujan simultaneously received MDA using dihydroartemesinin-piperaquine (DHA-PQ). Health facility data was used to monitor malaria case incidence rate and test positivity rates.ResultsIn the MDA + IRS arm, malaria incidence dropped by 83% (IRR: 0·17 (0.16–0.18); p < 0.001) in children under 5 year and by 78% (IRR: 0·22 (0.22–0.23); p < 0.001) in persons aged ≥ 5 years from the pre-intervention to the intervention period. In the IRS arm malaria incidence dropped by 47% (IRR: 0.53 (0.51, 0.56); p < 0.001) in children under 5 years and by 71% 0.29 (0.28, 0.30); p < 0.001) in persons aged ≥ 5 years. A drastic drop occurred immediately after the intervention after which cases slowly increased in both arms. Malaria test positivity rate (TPR) dropped at a rate of 21 (p = 0.003) percentage points per 1000 persons in the MDA + IRS arm compared to the IRS arm. There was a mean decrease of 60 (p-value, 0.040) malaria cases among children under five years and a mean decrease in TPR of 16·16 (p-value, 0.001) in the MDA + IRS arm compared to IRS arm.InterpretationMDA significantly reduced malaria burden among children < 5 years however the duration of this impact needs to be further investigated.

Asymptomatic and submicroscopic Plasmodium infections in an area before and during integrated vector control in Homa Bay, western Kenya

BackgroundLong-lasting insecticidal nets (LLINs) have been the primary vector control strategy until indoor residual spraying (IRS) was added in Homa Bay and Migori Counties in western Kenya. The objective of this study was to evaluate the impact of LLINs integrated with IRS on the prevalence of asymptomatic and submicroscopic Plasmodium infections in Homa Bay County.MethodsA two-stage cluster sampling procedure was employed to enroll study participants aged ≥ 6 months old. Four consecutive community cross-sectional surveys for Plasmodium infection were conducted in residents of Homa Bay county, Kenya. Prior to the start of the study, all study households received LLINs, which were distributed between June 2017 and March 2018. The first (February 2018) and second (June 2018) surveys were conducted before and after the first round of IRS (Feb–Mar 2018), while the third (February 2019) and fourth (June 2019) surveys were conducted before and after the second application of IRS (February–March 2019). Finger-prick blood samples were obtained to prepare thick and thin smears for microscopic determination and qPCR diagnosis of Plasmodium genus.ResultsPlasmodium spp. infection prevalence by microscopy was 18.5% (113/610) before IRS, 14.2% (105/737) and 3.3% (24/720) after the first round of IRS and 1.3% (11/849) after the second round of IRS (p < 0.0001). Submicroscopic (blood smear negative, qPCR positive) parasitaemia reduced from 18.9% (115/610) before IRS to 5.4% (46/849) after IRS (p < 0.0001). However, the proportion of PCR positive infections that were submicroscopic increased from 50.4% (115/228) to 80.7% (46/57) over the study period (p < 0.0001). Similarly, while the absolute number and proportions of microscopy positives which were asymptomatic decreased from 12% (73/610) to 1.2% (9/849) (p < 0.0001), the relative proportion increased. Geometric mean density of P. falciparum parasitaemia decreased over the 2-year study period (p < 0.0001).ConclusionsThese data suggest that two annual rounds of IRS integrated with LLINs significantly reduced the prevalence of Plasmodium parasitaemia, while the proportion of asymptomatic and submicroscopic infections increased. To reduce cryptic P. falciparum transmission and improve malaria control, strategies aimed at reducing the number of asymptomatic and submicroscopic infections should be considered.

Reduction in malaria burden following the introduction of indoor residual spraying in areas protected by long-lasting insecticidal nets in Western Kenya, 2016-2018.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria vector control measures deployed in Kenya. Widespread pyrethroid resistance among the primary vectors in Western Kenya has necessitated the re-introduction of IRS using an organophosphate insecticide, pirimiphos-methyl (Actellic® 300CS), as a pyrethroid resistance management strategy. Evaluation of the effectiveness of the combined use of non-pyrethroid IRS and LLINs has yielded varied results. We aimed to evaluate the effect of non-pyrethroid IRS and LLINs on malaria indicators in a high malaria transmission area. We reviewed records and tallied monthly aggregate of outpatient department (OPD) attendance, suspected malaria cases, those tested for malaria and those testing positive for malaria at two health facilities, one from Nyatike, an intervention sub-county, and one from Suba, a comparison sub-county, both located in Western Kenya, from February 1, 2016, through March 31, 2018. The first round of IRS was conducted in February-March 2017 in Nyatike sub-county and the second round one year later in both Nyatike and Suba sub-counties. The mass distribution of LLINs has been conducted in both locations. We performed descriptive analysis and estimated the effect of the interventions and temporal changes of malaria indicators using Poisson regression for a period before and after the first round of IRS. A higher reduction in the intervention area in total OPD, the proportion of OPD visits due to suspected malaria, testing positivity rate and annual malaria incidences were observed except for the total OPD visits among the under 5 children (59% decrease observed in the comparison area vs 33% decrease in the intervention area, net change -27%, P <0.001). The percentage decline in annual malaria incidence observed in the intervention area was more than twice the observed percentage decline in the comparison area across all the age groups. A marked decline in the monthly testing positivity rate (TPR) was noticed in the intervention area, while no major changes were observed in the comparison area. The monthly TPR reduced from 46% in February 2016 to 11% in February 2018, representing a 76% absolute decrease in TPR among all ages (RR = 0.24, 95% CI 0.12-0.46). In the comparison area, TPR was 16% in both February 2016 and February 2018 (RR = 1.0, 95% CI 0.52-2.09). A month-by-month comparison revealed lower TPR in Year 2 compared to Year 1 in the intervention area for most of the one year after the introduction of the IRS. Our findings demonstrated a reduced malaria burden among populations protected by both non-pyrethroid IRS and LLINs implying a possible additional benefit afforded by the combined intervention in the malaria-endemic zone.

Improving houses in the Bolivian Chaco increases effectiveness of residual insecticide spraying against infestation with Triatoma infestans, vector of Chagas disease

Failure to control domestic Triatoma infestans in the Chaco is attributed to vulnerable adobe construction, which provides vector refuges and diminishes insecticide contact. We conducted a pilot to test the impact of housing improvement plus indoor residual spraying (IRS) on house infestation and vector abundance in a rural community in the Bolivian Chaco. The intervention included three arms: housing improvement + IRS [HI], assisted IRS [AS] in which the team helped to clear the house pre-IRS and routine IRS [RS]. HI used locally available materials, traditional construction techniques and community participation. Vector parameters were assessed by Timed Manual Capture for 2 person-hours per house at baseline and medians of 114, 173, 314, 389 and 445days post-IRS-1. A second IRS round was applied at a median of 314days post-IRS-1. Post-intervention infestation indices and abundance fell in all three arms. The mean odds of infestation was 0.29 (95% CL 0.124, 0.684) in the HI relative to the RS arm. No difference was observed between AS and RS. Vector abundance was reduced by a mean 44% (24.8, 58.0) in HI compared to RS, with no difference between AS and RS. Median delivered insecticide concentrations per house were lower than the target of 50mg/m2 in >90% of houses in all arms. Housing improvement using local materials and community participation is a promising strategy to improve IRS effectiveness in the Bolivian Chaco. A larger trial is needed to quantify the impact on reinfestation over time.

A cost analysis to address issues of budget constraints on the implementation of the indoor residual spray programme in two districts of Maputo Province, Mozambique

BackgroundIt is frequently said that funding is essential to ensure optimal results from a malaria intervention control. However, in recent years, the capacity of the government of Mozambique to sustain the operational cost of indoor residual spraying (IRS) is facing numerous challenges due to restrictions of the Official Development Assistance. The purpose of the study was to estimate the cost of IRS operationalization in two districts of Maputo Province (Matutuíne and Namaacha) in Mozambique. The evidence produced in this study intends to provide decision-makers with insight into where they need to pay close attention in future planning in order to operationalize IRS with the existent budget in the actual context of budget restrictions.MethodsCost information was collected retrospectively from the provider perspective, and both economic and financial costs were calculated. A “one-way” deterministic sensitivity analysis was performed.ResultsThe average economic costs totaled US$117,351.34, with an average economic cost per household sprayed of US$16.35, and an average economic cost per person protected of US$4.09. The average financial cost totaled US$69,174.83, with an average financial cost per household sprayed and per person protected of US$9.84 and US$2.46, respectively. Vehicle, salary, and insecticide costs were the greatest contributors to overall cost in the economic and financial analysis, corresponding to 52%, 17%, and 13% in the economic analysis and 21%, 27%, and 22% in the financial analysis, respectively. The sensitivity analysis was adapted to a range of ± (above and under) 25% change. There was an approximate change of 14% in the average economic cost when vehicle costs were decreased by 25%. In the financial analysis, the average financial cost was lowered by 7% when salary costs were decreased by 25%.ConclusionsAltogether, the current cost analysis provides an impetus for the consideration of targeted IRS operationalization within the available governmental budget, by using locally-available human resources as spray operators to decrease costs and having IRS rounds be correctly timed to coincide with the build-up of vector populations.

Estimating the optimal interval between rounds of indoor residual spraying of insecticide using malaria incidence data from cohort studies.

Indoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We estimated the optimal timing interval for IRS using a statistical approach. Six rounds of IRS were implemented in Tororo District, a historically high malaria transmission setting in Uganda, during the study period (3 rounds with bendiocarb active ingredient (Ficam®): December 2014 to December 2015, and 3 rounds with pirimiphos methyl active ingredient (Actellic 300®CS): June 2016 to July 2018). A generalized additive model was used to estimate the optimal timing interval for IRS based on the predicted malaria incidence. The model was fitted to clinical incidence data from a cohort of children aged 0.5-10 years from selected households observed throughout the study period. 494 children, 67% aged less than 5 years at enrolment were analysed. Six-months period incidence of malaria decreased from 2.96 per person-years at the baseline to 1.74 following the first round of IRS and then to 0.02 after 6 rounds of IRS. The optimal time interval for IRS differed between bendiocarb and pirimiphos methyl and by IRS round. To retain an optimum impact, bendiocarb would require respraying 17 (95% CI: 14.2-21.0) weeks after application whereas pirimiphos methyl could remain impactful for 40 (95% CI: 37.0-42.8) weeks, although in the final year this estimates 36 (95% CI: 32.7-37.7) weeks. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of pirimiphos methyl. Neither the amount of rainfall nor the EIR nor the distribution of nets were found to be statistically significant for determining the time period between spray rounds. In our setting, the effect of the two IRS products was distinct. Statistically, pirimiphos methyl provided a longer window of protection than bendiocarb, although impact varied between different spray rounds and years which was not explained by rainfall or EIR or distribution of nets in our statistical approach. Understanding the effectiveness of IRS and how long it lasts can help for planning campaigns, but one should consider the financial cost and insecticide resistance. Monitoring the timing of spray campaigns using clinical incidence could be repeated in future programs to help determine the average period of protectivity of these products.

Recalibration of insecticide-measuring containers could prevent underdosing of insecticide during indoor residual spraying for visceral leishmaniasis (kala-azar) elimination in India.

The visceral leishmaniasis (kala-azar) elimination programme in India relies on indoor residual spraying (IRS) for sand-fly vector control. Insecticide supplied by a new manufacturer was introduced for IRS in 2019. We aimed to explore whether this led to a change in insecticide quantity being used in the field. We compared measurements of weights of 250mL of insecticide powder of two different manufacturers using a certified and calibrated weighing instrument. The density of insecticide supplied in 2019 was 43.4% lower than that in 2018, thereby leading to underdosing during current IRS activity. Insecticide-measuring containers should be recalibrated prior to every IRS round and also when an insecticide manufacturer changes, so that the insecticide dose is maintained within the recommended range.

The Impact of Control Interventions on Malaria Burden in Young Children in a Historically High-Transmission District of Uganda: A Pooled Analysis of Cohort Studies from 2007 to 2018.

.There is limited evidence on whether malaria elimination is feasible in high-transmission areas of Africa. Between 2007 and 2018, we measured the impact of malaria control interventions in young children enrolled in three clinical trials and two observational studies in Tororo, Uganda, a historically high-transmission area. Data were pooled from children aged 0.5–2 years. Interventions included individually assigned chemoprevention and repeated rounds of indoor residual spraying (IRS) of insecticide. All children received long-lasting insecticidal nets (LLINs) and treatment for symptomatic malaria with artemisinin-based combination therapy. Malaria incidence was measured using passive surveillance and parasite prevalence by microscopy and molecular methods at regular intervals. Poisson’s generalized linear mixed-effects models were used to estimate the impact of various control interventions. In total, 939 children were followed over 1,221.7 person years. In the absence of chemoprevention and IRS (reference group), malaria incidence was 4.94 episodes per person year and parasite prevalence 47.3%. Compared with the reference group, implementation of IRS was associated with a 97.6% decrease (95% CI: 93.3–99.1%, P = 0.001) in the incidence of malaria and a 96.0% decrease (95% CI: 91.3–98.2%, P < 0.001) in parasite prevalence (both measured after the fifth and sixth rounds of IRS). The addition of chemoprevention with monthly dihydroartemisinin–piperaquine to IRS was associated with a 99.5% decrease (95% CI: 98.6–99.9%, P < 0.001) in the incidence of malaria. In a historically high–malaria burden area of Uganda, a combination of LLINs, effective case management, IRS, and chemoprevention was associated with almost complete elimination of malaria in young children.

Kala-azar elimination in a highly-endemic district of Bihar, India: Asuccess story.

BackgroundVisceral leishmaniasis (VL) or Kala-azar has been a major public health problem in Bihar, India, for several decades. A few VL infected districts including Vaishali have reported >600 cases annually. Hence, in 2015, the Government of India entrusted ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna, to implement an integrated control strategy for achieving the VL elimination target (<1 case per 10,000 people at the block level) in the Vaishali District of Bihar.MethodologyThis study was conducted between January 2015 and December 2016. An integrated control strategy including the spatio-temporal mapping of VL-case distribution, active case detection, chemical-based vector control using indoor residual spraying (IRS), community awareness campaigns, the training of IRS members, the training of medical doctors for effective treatment, daily monitoring and the supervision of IRS activities, logistic management, post-IRS quality assurance, epidemiological surveillance, and entomological monitoring was performed. An insecticide quantification test was performed for evaluating the IRS quality on sprayed walls. A modern compression pump was used to maintain spray quality on different wall surfaces. The impact of IRS was assessed through sand fly collection in human dwellings and cattle sheds in pre- and post-IRS. The insecticide susceptibility of local P. argentipes was performed before each IRS round (in February and June) during 2015–2016. Statistical analysis such as the mean, percentage, and 95% CI were used to summarize the results.FindingsAll 16 blocks of the Vaishali District achieved the VL elimination target in 2016. The integrated VL control strategy helped reduce the number of VL cases from 664 in 2014 to 163 in 2016 and the number of endemic villages from 282 in 2014 to 142 in 2016. The case reduction rate was increased from 22.6% in 2014 to 58.8% in 2016. On average, 74 VL infected villages became Kala-azar free each year from 2015 to 2016.ConclusionsThe results of this study suggest that the elimination of VL is possible from all endemic blocks of Bihar if the integrated Vaishali VL control strategy is applied under strong monitoring and supervision.

Improving the performance of spray operators through monitoring and evaluation of insecticide concentrations of pirimiphos-methyl during indoor residual spraying for malaria control on Bioko Island

BackgroundQuality control of indoor residual spraying (IRS) is necessary to ensure that spray operators (SOs) deposit the correct concentration of insecticide on sprayed structures, while also confirming that spray records are not being falsified.MethodsUsing high-performance liquid chromatography (HPLC), this study conducted quality control of the organophosphate insecticide pirimiphos-methyl (Actellic 300CS), during the 2018 IRS round on Bioko Island, Equatorial Guinea. Approximately 60 SOs sprayed a total of 67,721 structures in 16,653 houses during the round. Houses that were reportedly sprayed were randomly selected for quality control testing. The SOs were monitored twice in 2018, an initial screening in March followed by sharing of results with the IRS management team and identification of SOs to be re-trained, and a second screening in June to monitor the effectiveness of training. Insecticide samples were adhesive-lifted from wooden and cement structures and analysed using HPLC.ResultsThe study suggests that with adequate quality control measures and refresher training, suboptimal spraying was curtailed, with a significant increased concentration delivered to the bedroom (difference = 0.36, P < 0.001) and wooden surfaces (difference 0.41, P = 0.001). Additionally, an increase in effective coverage by SOs was observed, improving from 80.7% in March to 94.7% in June after re-training (McNemar’s test; P = 0.03).ConclusionsThe ability to randomly select, locate, and test houses reportedly sprayed within a week via HPLC has led to improvements in the performance of SOs on Bioko Island, enabling the project to better evaluate its own performance.

The Impact of Multiple Rounds of Indoor Residual Spraying on Malaria Incidence and Hemoglobin Levels in a High-Transmission Setting.

Indoor residual spraying (IRS) is widely used as a vector control measure, although there are conflicting findings of its effectiveness in reducing malaria incidence. The objective of this study was to estimate the effect of multiple IRS rounds on malaria incidence and hemoglobin levels in a cohort of children in rural southeastern Uganda. The study was based upon a dynamic cohort of children aged 0.5-10 years enrolled from August 2011 to June 2017 in Nagongera Subcounty. Confirmed malaria infections and hemoglobin levels were recorded over time for each participant. After each of 4 rounds of IRS, malaria incidence, hemoglobin levels, and parasite density were evaluated and compared with pre-IRS levels. Analyses were carried out at the participant level while accounting for repeated measures and clustering by household. Incidence rate ratios comparing post-IRS to pre-IRS incidence rates for age groups 0-3, 3-5, and 5-11 were 0.108 (95% confidence interval [CI], .078-.149), 0.173 (95% CI, .136-.222), and 0.226 (95% CI, .187-.274), respectively. The mean hemoglobin levels significantly increased from 11.01 (pre-IRS) to 12.18 g/dL (post-IRS). Our study supports the policy recommendation of IRS usage in a stable and perennial transmission area to rapidly reduce malaria transmission.

The Impact of Control Interventions on Malaria Burden in a Historically High Transmission District of Uganda: A Pooled Analyses of Cohort Studies from 2007 to 2018

Background: There is limited evidence malaria elimination is feasible in high transmission areas of Africa. Between 2007-2018, we measured the impact of malaria control interventions in young children enrolled in three clinical trials and two observational studies in Tororo, Uganda, a historically high transmission area. Methods: Data were pooled from children aged 0.5-2 years. Interventions included individually assigned chemoprevention regimens and repeated rounds of indoor residual spraying of insecticide (IRS). All children received long-lasting insecticidal nets (LLINs) and treatment for symptomatic malaria with artemisinin-based combination therapy. Malaria incidence was measured using passive surveillance and parasite prevalence measured by microscopy and molecular methods at regular intervals. Poisson generalized linear mixed effects models were used to estimate the impact of various control interventions. Findings: 939 children were followed over 1221·7 person years. In the absence of chemoprevention and IRS (reference group), malaria incidence was 4·94 episodes per person year and parasite prevalence 47·3%. Compared to the reference group, implementation of the fifth and sixth rounds of IRS was associated with a 97·6% decrease (95% CI 93·3-99·1%, p=0·001) in the incidence of malaria and a 96·0% decrease (95% CI 91·3-98·2%, p<0·001) in parasite prevalence. The addition of chemoprevention with monthly dihydroartemisinin-piperaquine to IRS was associated with a 99·5% decrease (95% CI 98·6% to 99·9%, p<0·001) in the incidence of malaria. Interpretation: In a historically high malaria burden area of Uganda, a combination of LLINs, effective case management, IRS, and chemoprevention was associated with almost complete elimination of malaria in young children. Funding: Doris Duke Charitable Foundation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, Fogarty International Center. Declaration of Interest: All authors declare no competing interests. Ethical Approval: All studies were approved by the ethics committees of Makerere University, the Uganda National Council for Science and Technology, and the University of California San Francisco. Written informed consent was provided by parents/guardians for all study participants.

Comparative efficacy of two rounds of indoor residual spraying of DDT 75% @ 1g/m2 with that of DDT 50% @ 1g/m2 against the malaria vectors in India

While, dichlorodiphenyl-trichloroethane (DDT) water dispersible powder (WDP) 75% is considered as the high performance long lasting formulation for indoor residual spraying (IRS), no information is available regarding the comparative epidemiological effectiveness of the two DDT formulations when used for IRS in Indian conditions. The current study was undertaken to compare the effectiveness of IRS using DDT WDP 75% @ one g active ingredient (AI)/m2 with that using DDT WDP 50% @ one g AI/m2 in controlling Anopheles fluviatilis and An. culicifacies, the primary vectors of malaria in the selected endemic areas of Odisha State. Although, cone-bioassay mortality after 8 months of post spraying on DDT 75% sprayed surfaces as well as on sprayed but mud plastered surfaces was higher than DDT 50%, the six entomological parameters viz. resting density indoors and outdoors, trap density indoors, parous rate, human blood index and infection rate of An. fluviatilis and An. culicifacies did not show any statistically significant difference in reduction/ changes from pre- to post-spray period between the two DDT formulations.

Community facilitators and barriers to a successful implementation of mass drug administration and indoor residual spraying for malaria prevention in Uganda: a qualitative study

BackgroundThere is growing interest to add mass drug administration (MDA) to the already existing malaria prevention strategies, such as indoor residual spraying (IRS). However, successful MDA and IRS requires high population-wide coverage, emphasizing the importance of community acceptance. This study’s objectives were to identify community-level facilitators and barriers during the implementation of both MDA and IRS in communities with high malaria transmission intensity.MethodsThis was a qualitative study conducted in two sub-counties in Katakwi district. Kapujan sub-county residents received two rounds of IRS and MDA while Toroma sub-county residents received two rounds of IRS only. Key informant interviews and focus group discussions were conducted with key influential district and sub-county personnel and community members. Data were analysed using thematic analysis. Transcripts and interview notes from the in-depth interviews were analysed using a coding scheme developed from pre-defined topics together with themes emerging from the data. The Nvivo software program was used to aggregate the data by codes and to present study findings.ResultsOverall, 14 key informants were interviewed: 4 from Katakwi district and 5 each from Kapujan and Toroma sub-counties. Five focus group discussions were conducted: 4 with community members (men and women), 2 in each sub-county and one with medical staff of Toroma health centre IV. Important themes for consideration raised by the respondents include community sensitization, conducting implementation during the low activity dry season, involvement of government and local leadership, use of the competent locally composed team, community knowledge of malaria effects and consequences, combining interventions and evidence of malaria reduction from interventions. Potential barriers such as spreading of misinformation regarding interventions, the strong unpleasant smell from Actellic and inadequate duration of engagement with the community should be taken into consideration.ConclusionThis study documents important community engagement strategies that need to be considered when implementing malaria MDA in combination with IRS, for malaria prevention in such settings. This information is useful for malaria programmes, especially during the design and implementation of such community level interventions.

Persistent Parasitemia Despite Dramatic Reduction in Malaria Incidence After 3 Rounds of Indoor Residual Spraying in Tororo, Uganda.

Indoor residual spraying of insecticide (IRS) has been associated with reductions in the incidence of malaria, but its impact on malaria parasitemia is unclear. We followed 469 participants from August 2011 to May 2016 in Tororo, Uganda, a historically high malaria transmission setting. Three rounds of IRS with bendiocarb were implemented from December 2014 to December 2015. Symptomatic malaria episodes were identified by passive surveillance. Parasitemia was identified by active surveillance every 1-3 months using microscopy and Plasmodium falciparum-specific loop-mediated isothermal amplification. IRS was associated with a significant decline in the incidence of symptomatic malaria irrespective of age (episodes per person per year declined from 3.98 to 0.13 in children aged <5 years, 2.30 to 0.15 in children aged 5-10 years, and 0.41 to 0 in adults; P < .001 for all). IRS significantly reduced the prevalence of parasitemia, but the prevalence remained high (pre-IRS to post-third round: 58.5% to 11.3% in children aged <5 years, 73.3% to 23.7% in children aged 5-10 years, and 52.2% to 15.4% in adults; P < .001 for all). Although IRS was associated with significant reductions in the incidence of malaria and prevalence of parasitemia, a proportion of the population remained parasitemic, providing a potential reservoir for malaria transmission.

Genome-wide transcriptional analyses in Anopheles mosquitoes reveal an unexpected association between salivary gland gene expression and insecticide resistance

BackgroundTo combat malaria transmission, the Ugandan government has embarked upon an ambitious programme of indoor residual spraying (IRS) with a carbamate class insecticide, bendiocarb. In preparation for this campaign, we characterized bendiocarb resistance and associated transcriptional variation among Anopheles gambiae s.s. mosquitoes from two sites in Uganda.ResultsGene expression in two mosquito populations displaying some resistance to bendiocarb (95% and 79% An. gambiae s.l. WHO tube bioassay mortality in Nagongera and Kihihi, respectively) was investigated using whole-genome microarrays. Significant overexpression of several genes encoding salivary gland proteins, including D7r2 and D7r4, was detected in mosquitoes from Nagongera. In Kihihi, D7r4, two detoxification-associated genes (Cyp6m2 and Gstd3) and an epithelial serine protease were among the genes most highly overexpressed in resistant mosquitoes. Following the first round of IRS in Nagongera, bendiocarb-resistant mosquitoes were collected, and real-time quantitative PCR analyses detected significant overexpression of D7r2 and D7r4 in resistant mosquitoes. A single nucleotide polymorphism located in a non-coding transcript downstream of the D7 genes was found at a significantly higher frequency in resistant individuals. In silico modelling of the interaction between D7r4 and bendiocarb demonstrated similarity between the insecticide and serotonin, a known ligand of D7 proteins. A meta-analysis of published microarray studies revealed a recurring association between D7 expression and insecticide resistance across Anopheles species and locations.ConclusionsA whole-genome microarray approach identified an association between novel insecticide resistance candidates and bendiocarb resistance in Uganda. In addition, a single nucleotide polymorphism associated with this resistance mechanism was discovered. The use of such impartial screening methods allows for discovery of resistance candidates that have no previously-ascribed function in insecticide binding or detoxification. Characterizing these novel candidates will broaden our understanding of resistance mechanisms and yield new strategies for combatting widespread insecticide resistance among malaria vectors.

Rapid improvements to rural Ugandan housing and their association with malaria from intense to reduced transmission: a cohort study

SummaryBackgroundRapid population growth in Africa requires an urgent expansion and improvement of housing options. Improving housing presents a promising opportunity for malaria control by reducing indoor exposure to mosquitoes. We measured recent changes in house design in rural Uganda and evaluated their association with malaria in relation to a mass scale-up of control efforts.MethodsThis analysis was part of a cohort study designed to compare temporal changes in malaria incidence from a cohort of children and adults with temporal changes in malaria test positivity rate from health facility surveillance. All children aged 6 months to 10 years (n=384) living in 107 households in Nagongera sub-country, Tororo, Uganda, were given long-lasting insecticide-treated nets and followed between Aug 19, 2011, and June 30, 2017. Repeat rounds of indoor residual spraying of insecticide were initiated on Dec 5, 2014. Socioeconomic data were collected at two timepoints (Sept 25–Oct 9, 2013 and June 21–July 11, 2016) and houses were classified as modern (cement, wood, or metal walls, tiled or metal roof, and closed eaves) or traditional (all other homes). Associations between house design and three outcomes were evaluated before and after the introduction of indoor residual spraying: human biting rate estimated monthly in each household using US Centers for Disease Control and Prevention light traps; parasite prevalence measured routinely by microscopy every 3 months before indoor residual spraying and monthly after indoor residual spraying; and malaria incidence measured by passive surveillance.FindingsThe implementation of indoor residual spraying was associated with significant declines in human biting rate (33·5 vs 2·7 Anopheles per house per night after indoor residual spraying, p<0·0001), parasite prevalence (32·0% vs 14·0%, p<0·0001), and malaria incidence (3·0 vs 0·5 episodes per person-year at risk, p<0·0001). The prevalence of modern housing increased from 23·4% in 2013 to 45·4% in 2016 (p=0·001). Compared with traditional houses, modern houses were associated with a 48% reduction in human biting rate before indoor residual spraying (adjusted incidence rate ratio [aIRR] 0·52, 95% CI 0·36–0·73, p=0·0002), and a 73% reduction after indoor residual spraying (aIRR 0·27, 0·17–0·42, p<0·0001). Before indoor residual spraying, there was no association between house type and parasite prevalence, but after indoor residual spraying there was a 57% reduction in the odds of parasitaemia in modern houses compared with traditional houses, controlling for age, sex, and socioeconomic position (adjusted odds ratio 0·43, 95% CI 0·24–0·77, p=0·004). House type was not associated with malaria incidence before or after indoor residual spraying.InterpretationHouse design improved rapidly in rural Uganda and was associated with additional reductions in mosquito density and parasite prevalence following the introduction of indoor residual spraying. Changes to house design in endemic Africa, including closing eaves and the replacement of traditional building materials, might help further the gains achieved with more widely accepted malaria control interventions.FundingUS National Institutes of Health, Bill & Melinda Gates Foundation, and Medical Research Council UK.

Positive Influence of Behavior Change Communication on Knowledge, Attitudes, and Practices for Visceral Leishmaniasis/Kala-azar in India.

Visceral leishmaniasis (VL) is endemic to 54 districts in 4 states of India. Poor awareness of the disease and inappropriate health-seeking behavior are major challenges to eliminating the disease. Between February 2016 and March 2017, we implemented a behavior change communication (BCC) intervention in 33 districts of Bihar, 4 districts of Jharkhand, and 3 districts of West Bengal using a mix of channels, including group and interpersonal communication, to improve knowledge, attitudes, and practices of communities, frontline health workers, and opinion leaders. We conducted an impact assessment in October 2016, after the second indoor residual spraying (IRS) round, in Bihar and Jharkhand to evaluate the effect of the BCC intervention. Villages in 10 districts of Bihar and 4 districts in Jharkhand were selected for inclusion in the assessment. Selected villages were categorized as either intervention or control based on where project activities were conducted. Households were randomly selected proportional to caste composition, and interviewers surveyed the head of the household on whether the house was sprayed during the last IRS round and on knowledge, attitudes, and practices related to VL. We interviewed 700 households in intervention villages and 350 households in control villages and conducted correlation analysis to explore the association between IRS refusal and socioeconomic variables, and tested for association between IRS refusal and exposure to BCC activities. Odds ratios (ORs) were calculated. We reached an estimated 3.3 million contacts in Bihar and Jharkhand through the intervention's BCC activities. IRS refusal rates were significantly lower in intervention households than control households (mean=7.95% vs. 24.45%, respectively; OR, 0.27; 95% confidence interval [CI], 0.11 to 0.62; P<.001). Households in intervention villages were more aware than those in control villages that VL is spread by sand flies (68.4% vs. 7.4%, respectively; P<.001) and of IRS as an effective control measure (82.3% vs. 41.7%, respectively; P<.001). A greater percentage of households in intervention villages than control villages indicated they would encourage a patient to go to primary health centers for diagnosis and treatment of VL (77.0% vs. 39.4%, respectively) and to encourage others to accept IRS (78.6% vs. 44.6%, respectively; P<.001). Households that were exposed to community-based BCC activities largely using group and interpersonal communication had better knowledge, attitudes, and practices related to VL, including acceptance of IRS as a preventive measure, than households not exposed. BCC activities are thus an important component of VL elimination strategies.

Malaria in Tororo district after four rounds of indoor residual spraying: need to test and treat to prevent resurgence, Uganda, 2016

Introduction: in 2012, Tororo was a high malaria endemic district in Uganda with community Plasmodium prevalence of 71%. The Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and indoor Residual Spraying (IRS) in 2014 to control malaria in the district. We assessed malaria incidence, test positivity rates and Out-patient Department (OPD) attendance due to malaria before and after vector control interventions.

Resurgence of Malaria Following Discontinuation of Indoor Residual Spraying of Insecticide in an Area of Uganda With Previously High-Transmission Intensity.

Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the primary tools for malaria prevention in Africa. It is not known whether reductions in malaria can be sustained after IRS is discontinued. Our aim in this study was to assess changes in malaria morbidity in an area of Uganda with historically high transmission where IRS was discontinued after a 4-year period followed by universal LLIN distribution. Individual-level malaria surveillance data were collected from 1 outpatient department and 1 inpatient setting in Apac District, Uganda, from July 2009 through November 2015. Rounds of IRS were delivered approximately every 6 months from February 2010 through May 2014 followed by universal LLIN distribution in June 2014. Temporal changes in the malaria test positivity rate (TPR) were estimated during and after IRS using interrupted time series analyses, controlling for age, rainfall, and autocorrelation. Data include 65 421 outpatient visits and 13 955 pediatric inpatient admissions for which a diagnostic test for malaria was performed. In outpatients aged <5 years, baseline TPR was 60%-80% followed by a rapid and then sustained decrease to 15%-30%. During the 4-18 months following discontinuation of IRS, absolute TPR values increased by an average of 3.29% per month (95% confidence interval, 2.01%-4.57%), returning to baseline levels. Similar trends were seen in outpatients aged ≥5 years and pediatric admissions. Discontinuation of IRS in an area with historically high transmission intensity was associated with a rapid increase in malaria morbidity to pre-IRS levels.