Health economic evaluation of moist wound care in chronic cutaneous leishmaniasis ulcers in Afghanistan

Background: The present health economic evaluation in Afghanistan aims to support public health decision makers and health care managers to allocate resources efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited by Leishmania tropica or Leishmania major. Methods: A decision tree was used to analyse the cost and the effectiveness of two wound care regimens versus intra-lesional antimony in CL patients in Afghanistan. Costs were collected from a societal perspective. Effectiveness was measured in wound free days. The incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (NMB) were calculated. The model was parameterized with baseline parameters, sensitivity ranges, and parameter distributions. Finally, the model was simulated and results were evaluated with deterministic and probability sensitivity analyses. Final outcomes were the efficiency of the regimens and a budget impact analysis in the context of Afghanistan. Results: Average costs per patients were US$11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$ 16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound treatment [MWT]) and US$25 (SE = 0.48) (Group III: MWT) in patients with a single chronic CL ulcer. From a societal perspective the budget impact analysis shows that the regimens’ drug costs are lower than indirect disease cost. Average effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33) in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I was US$ 0.09 and Group III versus Group I US$0.77, which is very cost-effective with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte-Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of the cases starting at a willingness-to-pay of 80 cent per wound free day. Conclusions: Group II provided the most cost-effective treatment. The non-treatment alternative is not an option in the management of chronic CL ulcers. MWT of Group III should at least be practiced. The cost-effectiveness of Group III depends on the number of dressings necessary until complete wound closure

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation

International audienceINTRODUCTION: Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL).MATERIALS AND METHODS: Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings.RESULTS: Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized.CONCLUSIONS: The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments

Status of insecticide resistance in high-risk malaria provinces in Afghanistan

Background Insecticide resistance seriously threatens the efficacy of vector control interventions in malaria endemic countries. In Afghanistan, the status of insecticide resistance is largely unknown while distribution of long-lasting insecticidal nets has intensified in recent years. The main objective of this study was thus to measure the level of resistance to four classes of insecticides in provinces with medium to high risk of malaria transmission. Methods Adult female mosquitoes were reared from larvae successively collected in the provinces of Nangarhar, Kunar, Badakhshan, Ghazni and Laghman from August to October 2014. WHO insecticide susceptibility tests were performed with DDT (4 %), malathion (5 %), bendiocarb (0.1 %), permethrin (0.75 %) and deltamethrin (0.05 %). In addition, the presence of kdr mutations was investigated in deltamethrin resistant and susceptible Anopheles stephensi mosquitoes collected in the eastern provinces of Nangarhar and Kunar. Results Analyses of mortality rates revealed emerging resistance against all four classes of insecticides in the provinces located east and south of the Hindu Kush mountain range. Resistance is observed in both An. stephensi and Anopheles culicifacies, the two dominant malaria vectors in these provinces. Anopheles superpictus in the northern province of Badakhshan shows a different pattern of susceptibility with suspected resistance observed only for deltamethrin and bendiocarb. Genotype analysis of knock down resistance (kdr) mutations at the voltage-gated channel gene from An. stephensi mosquitoes shows the presence of the known resistant alleles L1014S and L1014F. However, a significant fraction of deltamethrin-resistant mosquitoes were homozygous for the 1014L wild type allele indicating that other mechanisms must be considered to account for the observed pyrethroid resistance. Conclusions This study confirms the importance of monitoring insecticide resistance for the development of an integrated vector management in Afghanistan. The validation of the kdr genotyping PCR assay applied to An. stephensi collected in Afghanistan paves the way for further studies into the mechanisms of insecticide resistance of malaria vectors in this region

Trends in malaria indicators after scale-up of community-based malaria management in Afghanistan.

BackgroundThe Community-Based Malaria Management (CBMM) strategy, introduced in 2013 and expanded to all health facilities and health posts in Afghanistan by 2016, aimed to deliver rapid diagnostic testing and more timely treatment to all communities nationwide. In this study, trends for several malaria outcome indicators were compared before and after the expansion of the CBMM strategy, using cross-sectional analysis of surveillance data.MethodsGeneralized estimating equation (GEE) models with a Poisson distribution were used to assess trends of three key outcomes before (2012-2015) and after (2016-2019) CBMM expansion. These outcomes were annual malaria incidence rate (both all and confirmed malaria incidence), malaria death rate, and malaria test positivity rate. Additional variables assessed included annual blood examination rates (ABER) and malaria confirmation rate.ResultsAverage malaria incidence rates decreased from 13.1 before CBMM expansion to 10.0 per 1000 persons per year after CBMM expansion (P < 0.001). The time period after CBMM was expanded witnessed a 339% increase in confirmed malaria incidence as compared to the period before (IRR 3.39, 95% CI 2.18, 5.27; P < 0.001). In the period since the expansion of CBMM (2016-2019), overall malaria incidence rate declined by 19% each year (IRR 0.81, 95% CI 0.71,0.92; P = 0.001) and the malaria death rate declined by 85% each year (IRR 0.15, 95% CI 0.12, 0.20; P < 0.001). In comparing the before period to the after period, the ABER increased from 2.3 to 3.5 per 100 person/year, the malaria test positivity rate increased from 12.2 to 20.5%, and the confirmation rate increased from 21% before to 71% after CBMM.ConclusionsAfghanistan's CBMM expansion to introduce rapid diagnostic tests and provide more timely treatment for malaria through all levels of care temporally correlates with significant improvement in multiple indicators of malaria control

Evaluation of point-of-care tests for cutaneous leishmaniasis diagnosis in Kabul, AfghanistanResearch in context

Background: Kabul (Afghanistan) is a major focus of cutaneous leishmaniasis (CL) caused by Leishmania tropica. Microscopy remains the reference test for diagnosis despite its low performance. We evaluated whether Loopamp™ Leishmania Detection Kit (Loopamp) and CL Detect™ Rapid Test (CL Detect), detecting Leishmania DNA and antigen, respectively could improve CL diagnosis. Methods: A diagnostic accuracy study with prospective inclusion was conducted in a leishmaniasis reference clinic in Kabul. Slit skin samples from CL suspects were analysed by microscopy. Samples taken with a dental broach were tested with CL Detect, Loopamp, and PCR. All samples were transferred to the Academic Medical Center (AMC, the Netherlands) for PCR and Loopamp analyses. The diagnostic performance of the tests was evaluated against a reference combining microscopy and PCR. Findings: 274 CL suspects were included in the study. In Kabul, CL Detect had a 65·4% sensitivity [95% Confidence Interval (CI): 59.2–71.2%] and a 100% specificity [95% CI: 80.5–100%], while these were 87.6% [95%CI: 82.9–91.3%] and 70.6% [95% CI: 44.0–89.7%] for Loopamp. At AMC the Loopamp's sensitivity (92.2% [95% CI: 88.2–95.2%]) and specificity (94.1% [95% CI: 71.3–99.8%]) were higher. An algorithm where CL Detect negative suspects would be tested by Loopamp yielded a 93.4% sensitivity [95% CI: 89.6–96.1%] and a 94.1% specificity [95% CI: 71.3–99.8%] when Loopamp's performance at AMC was used. Interpretation: The high specificity of CL Detect and the performance of Loopamp allow their use in a diagnostic algorithm that would minimize the number of CL patients referred for confirmation. Fund: Federal Ministry of Education and Research, Germany

Agreement on key parameters by OWCL and NWCL clinical researchers.

<p>‘Standardized’ criteria are those as proposed in the reference paper Olliaro et al, 2013⁹; ‘updated’ criteria are those resulting from the consultation.</p

Site characteristics in New World settings.

<p>Site characteristics in New World settings.</p

Site characteristics in Old World settings.

<p>Site characteristics in Old World settings.</p