Are Long-Lasting Insecticidal Nets Effective for Preventing Childhood Deaths among Non-Net Users? A Community-Based Cohort Study in Western Kenya

Background

Increasing the distribution and use of insecticide-treated nets (ITNs) in Sub-Saharan Africa has made controlling malaria with ITNs more practical. We evaluated community effects induced by ITNs, specifically long-lasting insecticidal nets (LLINs), under ordinary conditions in an endemic malaria area of Western Kenya.

Methods

Using the database from Mbita Health and Demographic Surveillance System (HDSS), children younger than 5 years old were assessed over four survey periods. We analyzed the effect of bed net usage, LLIN density and population density of young people around a child on all-cause child mortality (ACCM) rates using Cox PH models.

Results

During the study, 14,554 children were followed and 250 deaths were recorded. The adjusted hazard ratios (HRs) for LLIN usage compared with no net usage were not significant among the models: 1.08 (95%CI 0.76–1.52), 1.19 (95%CI 0.69–2.08) and 0.92 (95%CI 0.42–2.02) for LLIN users, untreated net users, and any net users, respectively. A significant increasing linear trend in risk across LLIN density quartiles (HR = 1.25; 95%CI 1.03–1.51) and a decreasing linear trend in risk across young population density quartiles among non-net user children (HR = 0.77; 95%CI 0.63–0.94) were observed.

Conclusions

Although our data showed that current LLIN coverage level (about 35%) could induce a community effect to protect children sleeping without bed nets even in a malaria-endemic area, it appears that a better system is needed to monitor the current malaria situation globally in order to optimize malaria control programs with limited resources.     

Comparison of the Laboratory Standard Washing Using CIPAC Washing Agent and the Domestic Washing on Three Recommended Types of Long-Lasting Insecticidal Mosquito Nets

Background

One of the best ways to prevent malaria is the use of insecticide-treated bed nets. Manufacturers pursue easier, safer and more efficient nets. Hence, many studies on the efficacy and wash resistance using World Health Organization standards have been reported. The commonly used detergent is “Savon de Marseille”, because it closely resembles actually used soaps. At the 54^th Collaborative International Pesticides Analytical Council (CIPAC) Technical Meeting in 2010, it was suggested to replace it by a standardized “CIPAC washing agent”. The aim of this study was to investigate the difference between a laboratory hand washing simulation using the CIPAC washing agent (method-1) and a domestic washing (method-2) on different bed nets, as well as the effect of the drying process on the release of active ingredient.

Methods

Interceptor®, Permanet®2.0 and Netprotect® nets were used in three treatments, each repeated 20 times. The first treatment included method-1 washing and indoor drying. The second treatment included method-2 washing and indoor drying. The third treatment used method-2 washing and UV-drying. The residual insecticide contents were determined using gas chromatography.

Results

The washing procedure and the number of washes have a significant effect on the release of active ingredient. Statistically, the two washing methods have the same effect on removing the active ingredient from the Interceptor® and Permanet®2.0 net, but a significantly different influence on the Netprotect® nets. The drying process has no significant effect on the insecticide.

Conclusion

Both washing procedures affected the amount of insecticide remaining on nets independently of the impregnation technology. The active ingredient decreases with the number of washing cycles following an exponential or logarithmic model for coated nets. The laboratory hand washing simulation had more impact on the decrease of active ingredient content of the Netprotect® nets. All net types seemed to be effectively protected against UV-light.     

Possession and Usage of Insecticidal Bed Nets among the People of Uganda: Is BRAC Uganda Health Programme Pursuing a Pro-Poor Path?

Background

The use of insecticidal bed nets is found to be an effective public health tool for control of malaria, especially for under-five children and pregnant women. BRAC, an indigenous Bangladeshi non-governmental development organization, started working in the East African state of Uganda in June 2006. As part of its efforts to improve the health and well-being of its participants, BRAC Uganda has been distributing long lasting insecticide-treated bed nets (LLIN) at a subsidized price through health volunteers since February 2008. This study was conducted in March-April 2009 to examine how equitable the programme had been in consistence with BRAC Uganda''s pro-poor policy.

Methodology/Principal Findings

Information on possession of LLINs and relevant knowledge on its proper use and maintenance was collected from households either with an under-five child and/or a pregnant woman. The sample included three villages from each of the 10 branch offices where BRAC Uganda''s community-based health programme was operating. Data were collected by trained enumerators through face-to-face interviews using a hand-held personal digital assistant (PDA). Findings reveal that the study population had superficial knowledge on malaria and its transmission, including the use and maintenance of LLINs. The households'' rate of possession of bed nets (41–59%), and the proportion of under-five children (17–19%) and pregnant women (25–27%) who reported sleeping under an LLIN were not encouraging. Inequity was observed in the number of LLINs possessed by the households, in the knowledge on its use and maintenance, and between the two programme areas.

Conclusions/Significance

The BRAC Uganda''s LLINs distribution at a subsidized price appeared to be inadequate and inequitable, and BRAC''s knowledge dissemination is insufficient for initiating preventive actions such as proper use of LLINs to interrupt malaria transmission. Findings contribute to the on-going debate on LLINs distribution in Africa and make a strong case for its free distribution.     

Combining Organophosphate Treated Wall Linings and Long-lasting Insecticidal Nets for Improved Control of Pyrethroid Resistant Anopheles gambiae

Background

New approaches to delivering insecticides need to be developed to improve malaria vector control. Insecticidal durable wall lining (DL) and net wall hangings (NWH) are novel alternatives to indoor residual spraying which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations.

Methods

Experimental hut trials were carried out in Valley du Kou, Burkina Faso to evaluate the efficacy of pirimiphos methyl treated DL and NWH either alone or in combination with LLINs against pyrethroid resistant Anopheles gambiae ss. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes to investigate the insecticide resistance management potential of the combination.

Results

The overall kdr and ace-1^R allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone (>95% vs 40%; P<0.001). Combining pyrethroid DL with LLINs did not show improvement in mortality (48%) compared to the LLIN alone (44%) (P>0.1). Combining p-methyl DL or NWH with LLINs reduced biting rates significantly (8–9%) compared to p-methyl DL and NWH alone (>40%) and killed all An gambiae that entered the huts. Mosquitoes bearing the ace-1^R gene were more likely to survive in huts with p-methyl DL alone (p<0.03) whereas all resistant and susceptible genotypes were killed by the combination.

Conclusion

P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could provide significant epidemiological benefits against a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1^R resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall lining would be worth developing.     

The clinical efficacy of artemether/lumefantrine (Coartem®)

Background

In March 2008, the Solomon Islands and Vanuatu governments raised the goal of their National Malaria Programmes from control to elimination. Vector control measures, such as indoor residual spraying (IRS) and long-lasting insecticidal bed nets (LLINs) are key integral components of this programme. Compliance with these interventions is dependent on their acceptability and on the socio-cultural context of the local population. These factors need to be investigated locally prior to programme implementation.

Method

Twelve focus group discussions (FGDs) were carried out in Malaita and Temotu Provinces, Solomon Islands in 2008. These discussions explored user perceptions of acceptability and preference for three brands of long-lasting insecticide-treated bed nets (LLINs) and identified a number of barriers to their proper and consistent use.

Results

Mosquito nuisance and perceived threat of malaria were the main determinants of bed net use. Knowledge of malaria and the means to prevent it were not sufficient to guarantee compliance with LLIN use. Factors such as climate, work and evening social activities impact on the use of bed nets, particularly in men. LLIN acceptability plays a varying role in compliance with their use in villages involved in this study. Participants in areas of reported high and year round mosquito nuisance and perceived threat of malaria reported LLIN use regardless of any reported unfavourable characteristics. Those in areas of low or seasonal mosquito nuisance were more likely to describe the unfavourable characteristics of LLINs as reasons for their intermittent or non-compliance. The main criterion for LLIN brand acceptability was effectiveness in preventing mosquito bites and malaria. Discussions highlighted considerable confusion around LLIN care and washing which may be impacting on their effectiveness and reducing their acceptability in Solomon Islands.

Conclusion

Providing LLINs that are acceptable will be more important for improving compliance in areas of low or seasonal mosquito nuisance and malaria transmission. The implications of these findings on malaria elimination in Solomon Islands are discussed.     

Bed Net Durability Assessments: Exploring a Composite Measure of Net Damage

Background

The durability of Long Lasting Insecticidal Nets (LLINs) in field conditions is of great importance for malaria prevention and control efforts; however, the physical integrity of the net fabric is not well understood making it challenging to determine overall effectiveness of nets as they age. The 2011 World Health Organization Pesticide Evaluation Scheme (WHOPES) guidelines provide a simple, standardized method using a proportional hole index (PHI) for assessing net damage with the intent to provide national malaria control programs with guidelines to assess the useful life of LLINS and estimate the rate of replacement.

Methods

We evaluated the utility of the PHI measure using 409 LLINs collected over three years in Nampula Province, Mozambique following a mass distribution campaign in 2008. For each LLIN the diameter and distance from the bottom of the net were recorded for every hole. Holes were classified into four size categories and a PHI was calculated following WHOPES guidelines. We investigate how the size, shape, and location of holes influence the PHI. The areas of the WHOPES defined categories were compared to circular and elliptical areas based on approximate shape and actual measured axes of each hole and the PHI was compared to cumulative damaged surface area of the LLIN.

Results

The damaged area of small, medium, large, and extra-large holes was overestimated using the WHOPES categories compared to elliptical areas using the actual measured axes. Similar results were found when comparing to circular areas except for extra-large holes which were underestimated. (Wilcoxon signed rank test of differences p< 0.0001 for all sizes). Approximating holes as circular overestimated hole surface area by 1.5 to 2 times or more. There was a significant difference in the mean number of holes < 0.5 cm by brand and there were more holes of all sizes on the bottom of nets than the top. For a range of hypothetical PHI thresholds used to designate a “failed LLIN”, roughly 75 to 80% of failed LLINs were detected by considering large and extra-large holes alone, but sensitivity varied by brand.

Conclusions

Future studies may refine the PHI to better approximate overall damaged surface area. Furthermore, research is needed to identify whether or not appropriate PHI thresholds can be used to deem a net no longer protective. Once a cutoff is selected, simpler methods of determining the effective lifespan of LLINs can help guide replacement strategies for malaria control programs.     

Use of Bed Nets and Factors That Influence Bed Net Use among Jinuo Ethnic Minority in Southern China

Background

Insecticide-treated nets (ITNs) are an integral part of vector control recommendations for malaria elimination in China. This study investigated the extent to which bed nets were used and which factors influence bed net use among Jinuo Ethnic Minority in China-Myanmar-Laos border areas.

Methods and Findings

This study combined a quantitative household questionnaire survey and qualitative semi-structured in-depth interviews (SDI). Questionnaires were administered to 352 heads of households. SDIs were given to 20 key informants. The bed net to person ratio was 1∶2.1 (i.e., nearly one net for every two people), however only 169 (48.0%) households owned at least one net and 623 (47.2%) residents slept under bed nets the prior night. The percentages of residents who regularly slept under nets (RSUN) and slept under nets the prior night (SUNPN) were similar (48.0% vs. 47.2%, P>0.05), however the percentage correct use of nets (CUN) was significantly lower (34.5%, P<0.0001). The annual cash income per person (ACIP) was an independent factor that influenced bed net use (P<0.0001), where families with an ACIP of {"type":"entrez-protein","attrs":{"text":"CNY10000","term_id":"895491745","term_text":"CNY10000"}}CNY10000 or more were much more likely to use nets. House type was strongly associated with bed net use (OR: 4.71, 95% CI: 2.81, 7.91; P<0.0001), where those with traditional wood walls and terracotta roofs were significantly more likely to use nets, and the head of household''s knowledge was an independent factor (OR: 5.04, 95% CI: 2.72, 9.35; P<0.0001), where those who knew bed nets prevent malaria were significantly more likely to use nets too.

Conclusions

High bed net availability does not necessarily mean higher coverage or bed net use. Household income, house type and knowledge of the ability of bed nets to prevent malaria are all independent factors that influence bed net use among Jinuo Ethnic Minority.     

Species Shifts in the Anopheles gambiae Complex: Do LLINs Successfully Control Anopheles arabiensis?

Introduction

High coverage of conventional and long-lasting insecticide treated nets (ITNs and LLINs) in parts of E Africa are associated with reductions in local malaria burdens. Shifts in malaria vector species ratio have coincided with the scale-up suggesting that some species are being controlled by ITNs/LLINs better than others.

Methods

Between 2005–2006 six experimental hut trials of ITNs and LLINs were conducted in parallel at two field stations in northeastern Tanzania; the first station was in Lower Moshi Rice Irrigation Zone, an area where An. arabiensis predominates, and the second was in coastal Muheza, where An. gambiae and An. funestus predominate. Five pyrethroids and one carbamate insecticide were evaluated on nets in terms of insecticide-induced mortality, blood-feeding inhibition and exiting rates.

Results

In the experimental hut trials mortality of An. arabiensis was consistently lower than that of An. gambiae and An. funestus. The mortality rates in trials with pyrethroid-treated nets ranged from 25–52% for An. arabiensis, 63–88% for An. gambiae s.s. and 53–78% for An. funestus. All pyrethroid-treated nets provided considerable protection for the occupants, despite being deliberately holed, with blood-feeding inhibition (percentage reduction in biting rates) being consistent between species. Veranda exiting rates did not differ between species. Percentage mortality of mosquitoes tested in cone bioassays on netting was similar for An. gambiae and An. arabiensis.

Conclusions

LLINs and ITNs treated with pyrethroids were more effective at killing An. gambiae and An. funestus than An. arabiensis. This could be a major contributing factor to the species shifts observed in East Africa following scale up of LLINs. With continued expansion of LLIN coverage in Africa An. arabiensis is likely to remain responsible for residual malaria transmission, and species shifts might be reported over larger areas. Supplementary control measures to LLINs may be necessary to control this vector species.     

Can Topical Insect Repellents Reduce Malaria? A Cluster-Randomised Controlled Trial of the Insect Repellent N,N-diethyl-m-toluamide (DEET) in Lao PDR

Background

Mosquito vectors of malaria in Southeast Asia readily feed outdoors making malaria control through indoor insecticides such as long-lasting insecticidal nets (LLINs) and indoor residual spraying more difficult. Topical insect repellents may be able to protect users from outdoor biting, thereby providing additional protection above the current best practice of LLINs.

Methods and Findings

A double blind, household randomised, placebo-controlled trial of insect repellent to reduce malaria was carried out in southern Lao PDR to determine whether the use of repellent and long-lasting insecticidal nets (LLINs) could reduce malaria more than LLINs alone. A total of 1,597 households, including 7,979 participants, were recruited in June 2009 and April 2010. Equal group allocation, stratified by village, was used to randomise 795 households to a 15% DEET lotion and the remainder were given a placebo lotion. Participants, field staff and data analysts were blinded to the group assignment until data analysis had been completed. All households received new LLINs. Participants were asked to apply their lotion to exposed skin every evening and sleep under the LLINs each night. Plasmodium falciparum and P. vivax cases were actively identified by monthly rapid diagnostic tests. Intention to treat analysis found no effect from the use of repellent on malaria incidence (hazard ratio: 1.00, 95% CI: 0.99–1.01, p = 0.868). A higher socio-economic score was found to significantly decrease malaria risk (hazard ratio: 0.72, 95% CI: 0.58–0.90, p = 0.004). Women were also found to have a reduced risk of infection (hazard ratio: 0.59, 95% CI: 0.37–0.92, p = 0.020). According to protocol analysis which excluded participants using the lotions less than 90% of the time found similar results with no effect from the use of repellent.

Conclusions

This randomised controlled trial suggests that topical repellents are not a suitable intervention in addition to LLINs against malaria amongst agricultural populations in southern Lao PDR. These results are also likely to be applicable to much of the Greater Mekong Sub-region.

Trial Registration

This trial is registered with number {"type":"clinical-trial","attrs":{"text":"NCT00938379","term_id":"NCT00938379"}}NCT00938379     

Community participation for malaria elimination in Tafea Province, Vanuatu: Part I. Maintaining motivation for prevention practices in the context of disappearing disease

Background

In Uganda, long-lasting insecticidal nets (LLIN) have been predominantly delivered through two public sector channels: targeted campaigns or routine antenatal care (ANC) services. Their combination in a mixed-model strategy is being advocated to quickly increase LLIN coverage and maintain it over time, but there is little evidence on the efficiency of each system. This study evaluated the two delivery channels regarding LLIN retention and use, and estimated the associated costs, to contribute towards the evidence-base on LLIN delivery channels in Uganda.

Methods

Household surveys were conducted 5-7 months after LLIN distribution, combining questionnaires with visual verification of LLIN presence. Focus groups and interviews were conducted to further investigate determinants of LLIN retention and use. Campaign distribution was evaluated in Jinja and Adjumani while ANC distribution was evaluated only in the latter district. Costs were calculated from the provider perspective through retrospective analysis of expenditure data, and effects were estimated as cost per LLIN delivered and cost per treated-net-year (TNY). These effects were calculated for the total number of LLINs delivered and for those retained and used.

Results

After 5-7 months, over 90% of LLINs were still owned by recipients, and between 74% (Jinja) and 99% (ANC Adjumani) were being used. Costing results showed that delivery was cheapest for the campaign in Jinja and highest for the ANC channel, with economic delivery cost per net retained and used of USD 1.10 and USD 2.31, respectively. Financial delivery costs for the two channels were similar in the same location, USD 1.04 for campaign or USD 1.07 for ANC delivery in Adjumani, but differed between locations (USD 0.67 for campaign delivery in Jinja). Economic cost for ANC distribution were considerably higher (USD 2.27) compared to campaign costs (USD 1.23) in Adjumani.

Conclusions

Targeted campaigns and routine ANC services can both achieve high LLIN retention and use among the target population. The comparatively higher economic cost of delivery through ANC facilities was at least partially due to the relatively short time this system had been in existence. Further studies comparing the cost of well-established ANC delivery with LLIN campaigns and other delivery channels are thus encouraged.     

How much does malaria vector control quality matter: the epidemiological impact of holed nets and inadequate indoor residual spraying

Background

Insecticide treated nets (ITN) and indoor residual spraying (IRS) are the two pillars of malaria vector control in Africa, but both interventions are beset by quality and coverage concerns. Data from three control programs were used to investigate the impact of: 1) the physical deterioration of ITNs, and 2) inadequate IRS spray coverage, on their respective protective effectiveness.

Methods

Malaria indicator surveys were carried out in 2009 and 2010 in Bioko Island, mainland Equatorial Guinea and Malawi to monitor infection with P.falciparum in children, mosquito net use, net condition and spray status of houses. Nets were classified by their condition. The association between infection and quality and coverage of interventions was investigated.

Results

There was reduced odds of infection with P.falciparum in children sleeping under ITNs that were intact (Odds ratio (OR): 0.65, 95% CI: 0.55–0.77 and OR: 0.81, 95% CI: 0.56–1.18 in Equatorial Guinea and in Malawi respectively), but the protective effect became less with increasingly worse condition of the net. There was evidence for a linear trend in infection per category increase in deterioration of nets. In Equatorial Guinea IRS offered protection to those in sprayed and unsprayed houses alike when neighbourhood spray coverage was high (≥80%) compared to those living in areas of low IRS coverage (<20%), regardless of whether the house they lived in was sprayed or not (adjusted OR = 0.54, 95% CI 0.33–0.89). ITNs provided only personal protection, offering no protection to non users. Although similar effects were seen in Malawi, the evidence was much weaker than in Equatorial Guinea.

Conclusions

Universal coverage strategies should consider policies for repair and replacement of holed nets and promote the care of nets by their owners. IRS programs should ensure high spray coverage since inadequate coverage gives little or no protection at all.     

Dry season determinants of malaria disease and net use in Benin, West Africa

Background

To achieve malaria eradication, control efforts have to be sustained even when the incidence of malaria cases becomes low during the dry season. In this work, malaria incidence and its determinants including bed net use were investigated in children of under 5 years of age in 28 villages in southern Benin during the dry season.

Methods and Findings

Mean malaria clinical incidence was measured in children aged 0–5 years by active case detection in 28 villages of the Ouidah-Kpomasse-Tori Bossito sanitary district between November 2007 and March 2008. Using Poisson mixed-effect models, malaria incidence was assessed according to the level of transmission by different vector species, and Long-Lasting Insecticide-treated mosquito Nets (LLIN) use and ownership. Then, a Binomial mixed-effect model was developed to assess whether nighttime temperature (derived from MODIS remote sensing data), biting nuisance and LLIN ownership are good predictors of LLIN use >60%. Results suggested that Anopheles funestus (Incidence Rates Ratio (IRR) = 3.38 [IC95 1.91–6]) rather than An. gambiae s.s. is responsible for malaria transmission. A rate of LLIN use >60% was associated with a lower risk of malaria (IRR = 0.6 [IC95 0.37–0.99]). Low nocturnal temperature and high biting nuisance were good predictors of LLIN use >60%.

Conclusions

As recommended by the Malaria Eradication (MalERA) Consultative Group on Modelling, there is a need to understand better the effects of seasonality on malaria morbidity. This study highlights the need to take into account the specificity of malaria epidemiology during the dry-hot season and get a better understanding of the factors that influence malaria incidence and net use. These findings should help National Malaria Control Programmes to implement more effective and sustainable malaria control strategies in Africa.     

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

Background

Malaria remains a major public health problem in Ethiopia. Pyrethroid-treated mosquito nets are one of the major tools available for the prevention and control of malaria transmission. PermaNet^® is a long-lasting insecticide-treated net (LLIN) recommended by WHO for malaria control.

Objective

The objective of the study was to assess utilization and retention of PermaNet^® nets distributed for malaria control in Buie and Fentalie districts and monitor the bio-efficacy of the nets using the WHO cone bioassay test procedures.

Methods

A cross sectional study was carried out by interviewing household heads or their representative in Buie and Fentalie districts. The two districts were selected based on a priori knowledge of variations on ethnic background and housing construction. Clusters of houses were chosen within each of the study villages for selection of households. 20 households that had received one or more PermaNet^® nets were chosen randomly from the clusters in each village. A total of eight used PermaNet^® nets were collected for the bio-efficacy test. The bio-efficacy of PermaNet^® nets was monitored according to the standard WHO procedures using a susceptible colony of Anopheles arabiensis to deltamethrin.

Results

A total of 119 household heads were interviewed during the study. The retention rate of nets that were distributed in 2005 and 2006 season was 72%. A total of 62.2% of the interviewees claimed children under five years of age slept under LLIN, while only 50.7% of the nets were observed to be hanged inside houses when used as a proxy indicator of usage of LLIN. For the bio-efficacy test the mean knock-down was 94% and 100%, while the mean mortality rate observed after 24 hr holding period was 72.2% and 67% for Buie and Fentalie districts respectively.

Conclusion

The study revealed a moderately high retention of PermaNet^® in the study villages and effectiveness of the nets when tested according to the standard WHO procedure.     

Population preference of net texture prior to bed net trial in Kala-Azar-endemic areas

Prior to a community-based efficacy trial of long-lasting insecticidal nets (LLINs) in the prevention of visceral leishmaniasis (VL; also called kala-azar), a pilot study on preference of tools was held in endemic areas of India and Nepal in September 2005.LLINs made of polyester and polyethylene were distributed to 60 participants, who used the nets sequentially for 7 d. Acceptability and preference were evaluated via indirect indicators through questionnaires at three defined time points before and after use of the LLINs and through focus group discussions (FGDs). In the latter, preferences for color and size were also assessed. Untreated bed nets were owned by 87% of the households prior to the study. All users liked textures of both LLIN types after 7 d of use, but had a slight preference for those made of polyester if they were to recommend a LLIN to relatives or friends (p<0.05), mainly because of their relatively greater softness in comparison to polyethylene LLINs. Users reported that both net types reduced mosquito bites and number of insects, including sand fly (bhusana; genus Phlebotomus), inside the house. Side effects were minor and disappeared quickly.The large-scale intervention trial considered the preferences of the study population to decide on the best tool of intervention--light-blue, rectangular, polyester LLINs of different sizes.     

The Impact of Artemisinin Combination Therapy and Long-Lasting Insecticidal Nets on Forest Malaria Incidence in Tribal Villages of India, 2006–2011

Introduction

New tools for malaria control, artemisinin combination therapy (ACT) and long-lasting insecticidal nets (LLINs) were recently introduced across India. We estimated the impact of universal coverage of ACT and ACT plus LLINs in a setting of hyperendemic, forest malaria transmission.

Methods

We reviewed data collected through active and passive case detection in a vaccine trial cohort of 2,204 tribal people residing in Sundargarh district, Odisha between 2006 and 2011. We compared measures of transmission at the village and individual level in 2006–2009 versus 2010–2011 after ACT (in all villages) and LLINs (in three villages) were implemented.

Results

During 2006–2009 malaria incidence per village ranged from 156–512 per 1000 persons per year and slide prevalence ranged from 28–53%. Routine indoor residual spray did not prevent seasonal peaks of malaria. Post-intervention impact in 2010–2011 was dramatic with ranges of 14–71 per 1000 persons per year and 6–16% respectively. When adjusted for village, ACT alone decreased the incidence of malaria by 83% (IRR 0.17, 95%CI: 0.10, 0.27) and areas using ACT and LLINs decreased the incidence of malaria by 86% (IRR 0.14, 95%CI: 0.05, 0.38). After intervention, the age of malaria cases, their parasite density, and proportion with fever at the time of screening increased.

Conclusions

ACT, and LLINs along with ACT, effectively reduced malaria incidence in a closely monitored population living in a forest ecotype. It is unclear whether LLINs were impactful when prompt and quality antimalarial treatment was available. In spite of universal coverage, substantial malaria burden remained.     

Malaria Transmission in Bissau,Guinea-Bissau between 1995 and 2012: Malaria Resurgence Did Not Negatively Affect Mortality

Introduction

As Plasmodium falciparum prevalence decreases in many parts of Sub-Saharan Africa, so does immunity resulting in larger at risk populations and increased risk of malaria resurgence. In Bissau, malaria prevalence decreased from ∼50% to 3% between 1995 and 2003. The epidemiological characteristics of P. falciparum malaria within Bandim health and demographic surveillance site (population ∼100000) between 1995 and 2012 are described.

Methods and Findings

The population was determined by census. 3603 children aged <15 years that were enrolled in clinical trials at the Bandim health centre (1995–2012) were considered incident cases. The mean annual malaria incidence per thousand children in 1995–1997, 1999–2003, 2007, 2011, 2012 were as follows; age <5 years 22→29→4→9→3, age 5–9 years 15→28→4→33→12, age 10–14 years 9→15→1→45→19. There were 4 campaigns (2003–2010) to increase use of insecticide treated bed nets (ITN) amongst children <5 years. An efficacious high-dose chloroquine treatment regime was routinely used until artemisinin based combination therapy (ACT) was introduced in 2008. Long lasting insecticide treated bed nets (LLIN) were distributed in 2011. By 2012 there was 1 net per 2 people and 97% usage. All-cause mortality decreased from post-war peaks in 1999 until 2012 in all age groups and was not negatively affected by malaria resurgence.

Conclusion

The cause of decreasing malaria incidence (1995–2007) was probably multifactorial and coincident with the use of an efficacious high-dose chloroquine treatment regime. Decreasing malaria prevalence created a susceptible group of older children in which malaria resurged, highlighting the need to include all age groups in malaria interventions. ACT did not hinder malaria resurgence. Mass distribution of LLINs probably curtailed malaria epidemics. All-cause mortality was not negatively affected by malaria resurgence.     

Modeling the Cost Effectiveness of Malaria Control Interventions in the Highlands of Western Kenya

Introduction

Tools that allow for in silico optimization of available malaria control strategies can assist the decision-making process for prioritizing interventions. The OpenMalaria stochastic simulation modeling platform can be applied to simulate the impact of interventions singly and in combination as implemented in Rachuonyo South District, western Kenya, to support this goal.

Methods

Combinations of malaria interventions were simulated using a previously-published, validated model of malaria epidemiology and control in the study area. An economic model of the costs of case management and malaria control interventions in Kenya was applied to simulation results and cost-effectiveness of each intervention combination compared to the corresponding simulated outputs of a scenario without interventions. Uncertainty was evaluated by varying health system and intervention delivery parameters.

Results

The intervention strategy with the greatest simulated health impact employed long lasting insecticide treated net (LLIN) use by 80% of the population, 90% of households covered by indoor residual spraying (IRS) with deployment starting in April, and intermittent screen and treat (IST) of school children using Artemether lumefantrine (AL) with 80% coverage twice per term. However, the current malaria control strategy in the study area including LLIN use of 56% and IRS coverage of 70% was the most cost effective at reducing disability-adjusted life years (DALYs) over a five year period.

Conclusions

All the simulated intervention combinations can be considered cost effective in the context of available resources for health in Kenya. Increasing coverage of vector control interventions has a larger simulated impact compared to adding IST to the current implementation strategy, suggesting that transmission in the study area is not at a level to warrant replacing vector control to a school-based screen and treat program. These results have the potential to assist malaria control program managers in the study area in adding new or changing implementation of current interventions.     

Importance of factors determining the effective lifetime of a mass, long-lasting, insecticidal net distribution: a sensitivity analysis

Background

Long-lasting insecticidal nets (LLINs) reduce malaria transmission by protecting individuals from infectious bites, and by reducing mosquito survival. In recent years, millions of LLINs have been distributed across sub-Saharan Africa (SSA). Over time, LLINs decay physically and chemically and are destroyed, making repeated interventions necessary to prevent a resurgence of malaria. Because its effects on transmission are important (more so than the effects of individual protection), estimates of the lifetime of mass distribution rounds should be based on the effective length of epidemiological protection.

Methods

Simulation models, parameterised using available field data, were used to analyse how the distribution's effective lifetime depends on the transmission setting and on LLIN characteristics. Factors considered were the pre-intervention transmission level, initial coverage, net attrition, and both physical and chemical decay. An ensemble of 14 stochastic individual-based model variants for malaria in humans was used, combined with a deterministic model for malaria in mosquitoes.

Results

The effective lifetime was most sensitive to the pre-intervention transmission level, with a lifetime of almost 10 years at an entomological inoculation rate of two infectious bites per adult per annum (ibpapa), but of little more than 2 years at 256 ibpapa. The LLIN attrition rate and the insecticide decay rate were the next most important parameters. The lifetime was surprisingly insensitive to physical decay parameters, but this could change as physical integrity gains importance with the emergence and spread of pyrethroid resistance.

Conclusions

The strong dependency of the effective lifetime on the pre-intervention transmission level indicated that the required distribution frequency may vary more with the local entomological situation than with LLIN quality or the characteristics of the distribution system. This highlights the need for malaria monitoring both before and during intervention programmes, particularly since there are likely to be strong variations between years and over short distances. The majority of SSA's population falls into exposure categories where the lifetime is relatively long, but because exposure estimates are highly uncertain, it is necessary to consider subsequent interventions before the end of the expected effective lifetime based on an imprecise transmission measure.     

Effect of Village-wide Use of Long-Lasting Insecticidal Nets on Visceral Leishmaniasis Vectors in India and Nepal: A Cluster Randomized Trial

Background

Visceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages.

Methods

A cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial—three intervention and three control clusters in both India and Nepal—were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration.

Findings

A random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%–42.5%) as measured by means of LTs.

Interpretation

The ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program.

Trial registration

ClinicalTrials.gov CT-2005-015374     

Balancing robustness against the dangers of multiple attractors in a Hopfield-type model of biological attractors

Background

Many chronic human diseases are of unclear origin, and persist long beyond any known insult or instigating factor. These diseases may represent a structurally normal biologic network that has become trapped within the basin of an abnormal attractor.

Methodology/Principal Findings

We used the Hopfield net as the archetypical example of a dynamic biological network. By progressively removing the links of fully connected Hopfield nets, we found that a designated attractor of the nets could still be supported until only slightly more than 1 link per node remained. As the number of links approached this minimum value, the rate of convergence to this attractor from an arbitrary starting state increased dramatically. Furthermore, with more than about twice the minimum of links, the net became increasingly able to support a second attractor.

Conclusions/Significance

We speculate that homeostatic biological networks may have evolved to assume a degree of connectivity that balances robustness and agility against the dangers of becoming trapped in an abnormal attractor.