Effect of insecticide-treated bed nets on visceral leishmaniasis incidence in Bangladesh. A retrospective cohort analysis.

BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease, transmitted by the sand fly species Phlebotomus argentipes in the Indian sub-continent. Effective vector control is highly desirable to reduce vector density and human and vector contact in the endemic communities with the aim to curtail disease transmission. We evaluated the effect of long lasting insecticide treated bed nets (LLIN) and bed nets impregnated with slow-release insecticide tablet K-O TAB 1-2-3 (jointly insecticide-treated nets or ITN) on VL incidence in a highly endemic sub-district (upazila) in Bangladesh. METHODS: Several distributions of LLIN or K-O TAB 1-2-3 for self-impregnation of bed nets at home took place in Fulbaria upazila, Mymensigh district from 2004 to 2008 under three research projects, respectively funded by CDC, Atlanta, USA (2004) and WHO-TDR, Geneva, Switzerland (2006 & 2008). We included all households (n = 8142) in the 20 villages that had benefited in the past from one of these interventions (1295 donated LLIN and 11,918 local bed nets impregnated with K-O TAB 1-2-3) in the "exposed cohort". We recruited a "non-exposed cohort" in villages with contemporaneously similar incidence rates who had not received such vector control interventions (7729 HHs from nine villages). In both cohorts, we visited all families house to house and ascertained any VL cases for the 3 year period before and after the intervention. We evaluated the incidence rate (IR) of VL in both cohorts as primary endpoint, applying the difference-in-differences method. RESULTS: The study identified 1011 VL cases (IR 140.47/10,000 per year [py]) before the intervention, of which 534 and 477 cases in the intervention and control areas respectively. The IR was 144.13/10,000 py (534/37050) and 136.59/10,000 py (477/34923) in the intervention and control areas respectively, with no significant difference (p = 0.3901) before the intervention. After the intervention, a total of 555 cases (IR 77.11/10,000 py) were identified of which 178 (IR 48.04/10,000 py) in the intervention and 377 (107.95/10,000 py) in the control area. The intervention area had a significant lower IR than the control area during follow up, rate difference = -59.91, p<0.0001. The IR during follow up was significantly reduced by 96.09/10,000 py in the intervention area (p<0.0001) and 28.63/10,000 py in control area (p<0.0001) compared to baseline. There was a strong and significant overall effect of the ITN intervention, δ = -67.45, p <0.0001. Sex (OR = 1.36, p<0.0001) and age (OR = 0.99, p<0.0001) also had a significant effect on VL incidence. Male had a higher risk of VL than female and one year increase in age decreased the likelihood of VL by about 0.92%. Two third of the VL incidence occurred in the age range 2 to 30 years (median age of VL patients was 17 years). CONCLUSION: VL incidence rate was significantly lower in the ITN intervention cohort compared to control in Bangladesh. Some bias due to more intense screen-and-treat activities or other interventions in the intervention area cannot be ruled out. Nonetheless, given their feasibility and sustainability, ITNs should be considered for integrated vector control during the maintenance phase of the VL elimination programme.

Indoor residual spraying for kala-azar vector control in Bangladesh: A continuing challenge.

BACKGROUND: Visceral leishmaniasis (VL) in the Indian subcontinent is a fatal disease if left untreated. Between 1994 to 2013, the Ministry of Health of Bangladesh reported 1,09,266 cases of VL and 329 VL related deaths in 37 endemic districts. Indoor residual spraying (IRS) using dichlorodiphenyltrichloroethane (DDT) was used by the national programme in the 1960s to control malaria. Despite findings of research trials demonstrating that the synthetic pyrethroid deltamethrin 5 WP was very effective at reducing vector densities, no national VL vector control operations took place in Bangladesh between 1999 to early 2012. In 2012, IRS using deltamethrin 5 WP was re-introduced by the national programme, which consisted of pre-monsoon spraying in eight highly endemic sub-districts (upazilas). The present study aims to evaluate the effectiveness of IRS on VL vectors, as well as the process and performance of the spraying activities by national programme staff. METHODS: Five highly endemic upazilas of Mymensingh district were purposively selected (Fulbaria, Trishal, Mukthagacha, Gaforgaon and Bhaluka) to conduct the present study using the WHO/TDR monitoring and evaluation tool kit. IRS operations, conducted by 136 squads/teams, and 544 spraymen, were observed using check lists and questionnaires included in the WHO/TDR monitoring and evaluation tool kit. A household (HH) acceptability survey of IRS was conducted in all study areas using a structured questionnaire in 600 HHs. To measure the efficacy of IRS, pre-IRS (two weeks prior) and post-IRS (at one and five months after), vector density was measured using CDC light traps for two consecutive nights. Bioassays, using the WHO cone-method, were carried out in 80 HHs (40 sprayed and 40 unsprayed) to measure the effectiveness of the insecticide on sprayed surfaces. RESULTS: Of the 544 spraymen interviewed pre-IRS, 60%, 3% and 37% had received training for one, two and three days respectively. During spraying activities, 64% of the spraying squads had a supervisor in 4 upazilas but only one upazila (Mukthagacha) achieved 100% supervision of squads. Overall, 72.8% of the spraying squads in the study upazilas had informed HHs members to prepare their houses prior to spraying. The required personal protective equipment was not provided by the national programme during our observations and the spraying techniques used by all sprayers were sub-standard compared to the standard procedure mentioned in the M&E toolkit. In the HH interviews, 94.8% of the 600 respondents said that all their living rooms and cattle sheds had been sprayed. Regarding the effectiveness measurements (i.e. reduction of vector densities), a total of 4132 sand flies were trapped in three intervals, of which 3310 (80.1%) were P. argentipes; 46.5% (1540) males and 53.5% (1770) females. At one month post-IRS, P. argentipes densities were reduced by 22.5% but the 5 months post-IRS reduction was only 6.4% for both male and female. The bioassay tests showed a mean corrected mortality of P. argentipes sand flies at one month post-IRS of 87.3% which dropped to 74.5% at 4 months post-IRS in three upazilas, which is below the WHO threshold level (80%). CONCLUSION: The national programme should conduct monitoring and evaluation activities to ensure high quality of IRS operations as a pre-condition for achieving a fast and sustained reduction in vector densities. This will continue to be important during the maintenance phase of VL elimination on the Indian subcontinent. Further research is needed to determine other suitable vector control option(s) when the case numbers are very low.

Susceptibility of field-collected Phlebotomus argentipes (Diptera: Psychodidae) sand flies from Bangladesh and Nepal to different insecticides.

BACKGROUND: The sand fly Phlebotomus argentipes is the vector for visceral leishmaniasis (VL) in the Indian sub-continent. In Bangladesh since 2012, indoor residual spraying (IRS) was applied in VL endemic areas using deltamethrin. In Nepal, IRS was initiated in 1992 for VL vector control using lambda-cyhalothrin. Irrational use of insecticides may lead to vector resistance but very little information on this subject is available in both countries. The objective of this study was to generate information on the susceptibility of the vector sand fly, P. argentipes to insecticide, in support of the VL elimination initiative on the Indian sub-continent. METHODS: Susceptibility tests were performed using WHO test kits following the standard procedures regarding alpha cypermethrin (0.05%), deltamethrin (0.05%), lambda-cyhalothrin (0.05%), permethrin (0.75%), malathion (5%) and bendiocarb (0.1%) in six upazilas (sub-districts) in Bangladesh. In Nepal, the tests were performed for two insecticides: alpha cypermethrin (0.05%) and deltamethrin (0.05%). Adult P. argentipes sand flies were collected in Bangladesh from six VL endemic upazilas (sub-districts) and in Nepal from three endemic districts using manual aspirators. RESULTS: The results show that VL vectors were highly susceptible to all insecticides at 60 minutes of exposure in both countries. In Bangladesh, corrected mortality was 100% at 15 minutes as well as 30 minutes of exposure. The study sites in Nepal, however, showed some diverse results, with a mortality rate less than 90% for 15 minutes of exposure with alpha cypermethrin and deltamethrin in two districts but was above 95% after 30 minutes of exposure. CONCLUSIONS: These results suggest that the insecticides tested can still be used in the national programmes of Bangladesh and Nepal. However, insecticide rotation should be performed to mitigate the possible development of insecticide resistance. Periodic susceptibility tests should be performed by the countries to get timely alerts regarding insecticide resistance.

Control of Phlebotomus argentipes (Diptera: Psychodidae) sand fly in Bangladesh: A cluster randomized controlled trial.

BACKGROUND: A number of studies on visceral leishmaniasis (VL) vector control have been conducted during the past decade, sometimes came to very different conclusion. The present study on a large sample investigated different options which are partially unexplored including: (1) indoor residual spraying (IRS) with alpha cypermethrin 5WP; (2) long lasting insecticide impregnated bed-net (LLIN); (3) impregnation of local bed-nets with slow release insecticide K-O TAB 1-2-3 (KOTAB); (4) insecticide spraying in potential breeding sites outside of house using chlorpyrifos 20EC (OUT) and different combinations of the above. METHODS: The study was a cluster randomized controlled trial where 3089 houses from 11 villages were divided into 10 sections, each section with 6 clusters and each cluster having approximately 50 houses. Based on vector density (males plus females) during baseline survey, the 60 clusters were categorized into 3 groups: (1) high, (2) medium and (3) low. Each group had 20 clusters. From these three groups, 6 clusters (about 300 households) were randomly selected for each type of intervention and control arms. Vector density was measured before and 2, 4, 5, 7, 11, 14, 15, 18 and 22 months after intervention using CDC light traps. The impact of interventions was measured by using the difference-in-differences regression model. RESULTS: A total of 17,434 sand flies were collected at baseline and during the surveys conducted over 9 months following the baseline measurements. At baseline, the average P. argentipes density per household was 10.6 (SD = 11.5) in the control arm and 7.3 (SD = 8.46) to 11.5 (SD = 20.2) in intervention arms. The intervention results presented as the range of percent reductions of sand flies (males plus females) and rate ratios in 9 measurements over 22 months. Among single type interventions, the effect of IRS with 2 rounds of spraying (applied by the research team) ranged from 13% to 75% reduction of P. argentipes density compared to the control arm (rate-ratio [RR] ranged from 0.25 to 0.87). LLINs caused a vector reduction of 9% to 78% (RR, 0.22 to 0.91). KOTAB reduced vectors by 4% to 73% (RR, 0.27 to 0.96). The combination of LLIN and OUT led to a vector reduction of 26% to 86% (RR, 0.14 to 0.74). The reduction for the combination of IRS and OUT was 8% to 88% (RR, 0.12 to 0.92). IRS and LLIN combined resulted in a vector reduction of 13% to 85% (RR, 0.15 to 0.77). The IRS and KOTAB combination reduced vector densities by 16% to 86% (RR, 0.14 to 0.84). Some intermediate measurements for KOTAB alone and for IRS plus LLIN; and IRS plus KOTAB were not statistically significant. The bioassays on sprayed surfaces or netting materials showed favourable results (>80% mortality) for 22 months (IRS tested for 12 months). In the KOTAB, a gradual decline was observed after 6 months. CONCLUSIONS: LLIN and OUT was the best combination to reduce VL vector densities for 22 months or longer. Operationally, this is much easier to apply than IRS. A cost analysis of the preferred tools will follow. The relationship between vector density (males plus females) and leishmaniasis incidence should be investigated, and this will require estimates of the Entomological Inoculation Rate.

Toolkit for monitoring and evaluation of indoor residual spraying for visceral leishmaniasis control in the Indian subcontinent: application and results.

Background. We field tested and validated a newly developed monitoring and evaluation (M&E) toolkit for indoor residual spraying to be used by the supervisors at different levels of the national kala-azar elimination programs in Bangladesh, India and Nepal. Methods. Methods included document analysis, in-depth interviews, direct observation of spraying squads, and entomological-chemical assessments (bioassay, susceptibility test, chemical analysis of insecticide residues on sprayed surfaces, vector density measurements at baseline, and three follow-up surveys). Results. We found that the documentation at district offices was fairly complete; important shortcomings included insufficient training of spraying squads and supervisors, deficient spray equipment, poor spraying performance, lack of protective clothing, limited coverage of houses resulting in low bioavailability of the insecticide on sprayed surfaces, and reduced vector susceptibility to DDT in India, which limited the impact on vector densities. Conclusion. The M&E toolkit is a useful instrument for detecting constraints in IRS operations and to trigger timely response.