Triple-drug therapy with ivermectin, diethylcarbamazine and albendazole for the acceleration of lymphatic filariasis elimination in Kenya: Programmatic implementation and results of the first impact assessment.

The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after the two annual rounds of mass treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic.

Model-based geostatistical design and analysis of prevalence for soil-transmitted helminths in Kenya: Results from ten-years of the Kenya national school-based deworming programme.

Background: Kenya is endemic for soil-transmitted helminths (STH) with over 6 million children in 27 counties currently at-risk. A national school-based deworming programme (NSBDP) was launched in 2012 with a goal to eliminate parasitic worms as a public health problem. This study used model-based geostatistical (MBG) approach to design and analyse the impact of the NSBDP and inform treatment strategy changes. Methods: A cross-sectional study was used to survey 200 schools across 27 counties in Kenya. The study design, school selection and analysis followed the MBG approach which incorporated historical data on treatment, morbidity and environmental covariates to efficiently predict the helminths prevalence in Kenya. Results: Overall, the NSBDP geographic area prevalence for any STH was estimated to sit between 2 % and <10 % with a high predictive probability of >0.999. Species-specific thresholds were between 2 % and <10 % for Ascaris lumbricoides, 0 % to <2 % for hookworm, and 0 % to <2 % for Trichuris trichiura, all with high predictive probability of >0.999. Conclusions: Based on the World Health Organization guidelines, STH treatment requirements can now be confidently refined. Ten counties may consider suspending treatment and implement appropriate surveillance system, while another 10 will require treatment once every two years, and the remaining seven will require treatment once every year.

Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study.

INTRODUCTION: Dual diethylcarbamazine and albendazole (DA) therapy is the standard mass drug administration (MDA) regimen for lymphatic filariasis in Kenya. Following the recent World Health Organization recommendation, Kenya piloted triple therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in MDA. OBJECTIVE: We conducted a community-based, observational, cohort event monitoring study to compare the types, frequency, severity, and predictors of adverse events following dual versus triple therapy in 20,421 eligible residents. METHODS: Residents in Kilifi (n = 10,010) and Mombasa counties (n = 10,411) received DA and IDA through MDA campaigns, respectively. Adverse events were actively monitored through house-to-house visits on days 1, 2, and 7 after MDA. Any clinical events reported before and after MDA were cross-checked and verified to differentiate pre-existing events from MDA-associated adverse events. RESULTS: Overall, 5807 and 3102 adverse events were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more adverse events was significantly higher (p < 0.0001) in the IDA group (27.3%; 95% confidence interval [CI] 26.4-28.2) than in the DA group (16.2%; 95% CI 15.5-16.9). Dizziness (15.9% vs 5.9%) and drowsiness (10.1% vs 2.6%) were the most common adverse events and significantly higher in the IDA group compared with the DA group (p < 0.0001). Most adverse events were mild or moderate with a few severe cases (IDA = 0.05%; 95% CI 0.35-0.78, DA = 0.03%; 95% CI 0.14-0.60). Female sex, obesity, taking three or more diethylcarbamazine or ivermectin tablets, and having pre-existing clinical symptoms were significant predictors of adverse events following IDA treatment. CONCLUSIONS: Ivermectin, diethylcarbamazine, and albendazole as a combination is as safe and well tolerated as DA to use in MDA campaigns with no serious life-threatening adverse events. Systemic mild-to-moderate adverse events with a few severe cases and transient adverse events are more common with IDA treatment than with DA treatment. Hence, integrating pharmacovigilance into a MDA program is recommended for the timely detection and management of adverse events.

Geostatistical modelling of the distribution, risk and burden of podoconiosis in Kenya.

BACKGROUND: Understanding and accurately predicting the environmental limits, population at risk and burden of podoconiosis are critical for delivering targeted and equitable prevention and treatment services, planning control and elimination programs and implementing tailored case finding and surveillance activities. METHODS: This is secondary analysis of a nationwide podoconiosis mapping survey in Kenya. We combined national representative prevalence survey data of podoconiosis with climate and environmental data, overlayed with population figures in a geostatistical modelling framework, to predict the environmental suitability, population living in at-risk areas and number of cases of podoconiosis in Kenya. RESULTS: In 2020, the number of people living with podoconiosis in Kenya was estimated to be 9344 (95% uncertainty interval 4222 to 17 962). The distribution of podoconiosis varies by geography and three regions (Eastern, Nyanza and Western) represent >90% of the absolute number of cases. High environmental suitability for podoconiosis was predicted in four regions of Kenya (Coastal, Eastern, Nyanza and Western). In total, 2.2 million people live in at-risk areas and 4.2% of the total landmass of Kenya is environmentally predisposed for podoconiosis. CONCLUSIONS: The burden of podoconiosis is relatively low in Kenya and is mostly restricted to certain small geographical areas. Our results will help guide targeted prevention and treatment approaches through local planning, spatial targeting and tailored surveillance activities.

Towards elimination of Lymphatic Filariasis in Kenya: improving advocacy, communication and social mobilization activities for mass drug administration, a qualitative study.

INTRODUCTION: The Kenya Breaking Transmission Strategy for Neglected Tropical Diseases (NTD) from 2019 to 2023 intensifies advocacy, coordination, and partnerships. The purpose of this study was to explore views and experiences of stakeholders and health workers on ways of improving the Advocacy, Communication and Social Mobilization (ACSM) activities of Mass Drug Administration (MDA) for Lymphatic Filariasis (LF) programs through participatory approaches in Kilifi County, Kenya. METHODS: Two wards were purposely selected in the Kaloleni sub-county, Kilifi County, where there was an average treatment coverage of 56% in 2015, 50.5% in 2016. Qualitative data collection methods were employed, which included participatory meetings with county stakeholders to understand their views, experiences, and suggestions on how ACSM strategies can be improved in MDA for LF. Twelve In-Depth Interviews (IDIs) were conducted (six with opinion leaders and six with Community Health Extension Workers (CHEWs) and two semi-structured interviews (SSIs) were held with county and sub-county coordinators involved in MDA administration. The aim was to better to understand their perceptions of the NTD program about ACSM, challenges to ACSM strategies, and ways to improve the strategies for ACSM in MDA for LF. The Data was organized and classified into codes and themes using QSR NVIVO version 12. RESULTS: The study observed the low participation of stakeholders in the ACSM activities of MDA for LF and identified potential areas for stakeholders' involvement to strengthen the activities. Challenges hindering effective implementation of ACSM activities include late delivery of Information, Educational and Communication (IEC) and few IEC materials, insufficient funding, inadequate time allocated to reach the assigned households with messages, messaging, and packaging of information for dissemination due to the vastness of the area. The stakeholders recommended innovative strategies and techniques to improve ACSM activities. DISCUSSION AND CONCLUSION: The results of this study show key challenges to ACSM implementation of MDA for LF. Implementers need to pay attention to these challenges to enhance the effectiveness of MDA per the Kenya NTD Breaking Transmission Strategy. ACSM efforts in MDA for LF control and elimination should be linked with overarching efforts to mainstream partnerships and coordination in control and elimination.

Mapping of Podoconiosis Cases and Risk Factors in Kenya: A Nationwide Cross-sectional Study.

Podoconiosis is a type of tropical lymphedema that is clinically distinguished from lymphatic filariasis (LF) because it is ascending and commonly bilateral but asymmetric. The disease is a result of a genetically determined inflammatory reaction to long-term exposure to mineral particles in irritant red clay soils derived mainly from volcanic soils. We conducted the first nationwide mapping of the prevalence and risk factors of podoconiosis in Kenya. We performed a population-based cross-sectional survey to determine the national prevalence of podoconiosis and included 6,228 individuals from 48 villages in 24 sub-counties across 15 counties. Participants answered a questionnaire about the history of symptoms compatible with podoconiosis, received a point-of-care antigen test, and underwent a physical examination if they had lymphedema. A confirmed case of podoconiosis was defined as a case in a resident of the study village who had lower limb bilateral and asymmetric lymphedema lasting more than 1 year, negative test results for Wuchereria bancrofti antigen, and other causes of lymphedema ruled out. Of all the individuals surveyed, 89 had lymphedema; of those, 16 of 6228 (0.3%; 95% confidence interval [CI], 0.1-0.5) were confirmed to have podoconiosis. A high prevalence of podoconiosis was found in western (Siaya, 3.1%; Busia, 0.9%) and central (Meru, 1.1%) regions, and a low prevalence was observed in northern (Marsabit, 0.2%), eastern (Makueni, 0.2%), and coastal (Tana River, 0.1%) regions. The identified risk factors were age 56 years or older (adjusted odds ratio [aOR], 5.66; 95% CI, 2.32-13.83; P < 0.001) and rarely wearing shoes (aOR, 18.92; 95% CI, 4.55-78.71; P < 0.001). These results indicated that the podoconiosis prevalence is low and localized in Kenya; therefore, elimination is achievable if appropriate disease prevention, management, and behavioral strategies are promoted.

Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study.

Preventive chemotherapy with diethylcarbamazine citrate (DEC) and albendazole (ALB) is the core intervention strategy to eliminate lymphatic filariasis (LF). We conducted a large-scale prospective active safety surveillance study to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass drug administration (MDA) of single-dose DEC and ALB in 10,010 participants from Kilifi County, Kenya. AEs were actively monitored and graded at 24 h, 48 h, and on day 7 Post-MDA. Out of 10,010 enrolled study participants, 1621 participants reported a total of 3102 AEs during a seven-day follow-up. The cumulative incidence of AEs was 16.2% (95% CI, 15.5-16.9%). The proportion of participants who experienced one, two, or ≥three types of AEs was 9.2%, 4.6%, 2.4%, respectively. AEs were mild (87.3%), moderate (12.4%), and severe (0.3%) and resolved within 72 h. The five most common AEs were dizziness (5.9%), headache (5.6%), loss of appetite (3.3%), fever (2.9%), and drowsiness (2.6%). Older age, taking concurrent medications, ≥three tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. One in six participants experienced systemic mild-to-moderate severity grading and transient AEs. DEC and ALB co-administration for the elimination of LF is generally safe and well-tolerated.

Implementation challenges and opportunities for improved mass treatment uptake for lymphatic filariasis elimination: Perceptions and experiences of community drug distributors of coastal Kenya.

Community drug distributors (CDDs) who are volunteers have the responsibility of awareness creation, household census, drug distribution and record-keeping and are thus key stakeholders in the campaign for Lymphatic Filariasis (LF) elimination. Taking into account their experiences and perceptions is important for a successful elimination campaign. We conducted a qualitative study in 2018 to identify implementation challenges and opportunities for improved mass drug administration (MDA) uptake based on the CDDs perceptions and experiences. Within a larger study that used mixed methods quasi-experimental design, we collected qualitative data from two wards in Kaloleni Sub-County of Kilifi County which was purposively selected owing to its low, 56% and 50.5% treatment coverage in 2015 and 2016 respectively. Focus group discussions (FGDs) (n = 8) and in-depth interviews (IDIs) (n = 8) with CDDs, IDIs (n = 22) with opinion leaders and IDIs (n = 8) with health workers were conducted and the data analyzed by QSR NVIVO version 10 according to thematic areas. The results showed that based on the perceptions and experiences of the CDDs, several challenges: communities' refusal to take the drugs; absenteeism during MDA; non-adherence to CDDs selection criteria; inadequacy in number of CDDs engaged during the campaign and training provided; insufficiency of drugs issued to CDDs; lack of CDDs supervision and low motivation negatively impact on MDA uptake. Opportunities to address the challenges included: awareness creation on MDA, health education on LF and observation of hygiene during drug administration, increased duration of awareness creation and drug administration, adherence to CDDs selection criteria and putting into consideration the vastness of an area and population density while deploying CDDs. Other opportunities include: improved CDDs training and scheduling; issuing of enough drugs to CDDs to meet the communities' demand and improved supervision and motivation of CDDs. Addressing the challenges highlighted is an important step of maximizing MDA uptake. The opportunities presented need to be considered by the NTD program personnel, the county health personnel and the community while planning the implementation of MDA campaigns.

Addressing barriers of community participation and access to mass drug administration for lymphatic filariasis elimination in Coastal Kenya using a participatory approach.

Since the prioritization of Lymphatic Filariasis (LF) elimination in 1997, progress has been made in reducing disease transmission and burden. Validation of elimination through Transmission Assessment Surveys (TAS) in implementation units (IUs) that have received at least 5 rounds of mass drug administration (MDA) and achieved minimum threshold of 65% treatment coverage is required. There are IUs that do not qualify for TAS due to achievement of low treatment coverage. This study sought to identify barriers of community participation and access to MDA, develop and test strategies to be recommended for improved uptake. Two wards in Kaloleni sub-county, Kilifi county with an average treatment coverage of 56% in 2015, 50.5% in 2016 were purposively sampled and a quasi-experimental study conducted. Through systematic random sampling, 350 (pre-intervention) and 338 (post-intervention) household heads were selected and interviewed for quantitative data. For qualitative data, 16 Focus Group Discussions (FGDs) with purposively selected community groups were conducted. Participatory meetings were held with county stakeholders to agree on strategies for improved community participation in MDA. The quantitative data were analyzed using STATA version 14.1, statistical significance assessed by chi square test and qualitative data by QSR NVIVO version 10. The identified strategies were tested in experimental sites during the 2018 MDA and the usual MDA strategies applied in control sites. The results showed an increase in community participation and access to MDA in both sites 80.6% (pre-intervention), 82.9% (post-intervention). The proportion of participants who considered the treatment as necessary significantly (p = 0.001) increased to 96.2% from 88.3% and significantly dropped for those with drug swallowing problems associated with: size (p<0.001), number (p<0.027) and taste (p = 0.001). The implemented strategies may have contributed to increased participation and access to MDA and should be applied for improved treatment uptake. Health education on disease aetiology and importance of drug uptake in all rounds is key to program's success.

Differential response to plant- and human-derived odorants in field surveillance of the dengue vector, Aedes aegypti.

Linalool oxide (LO) and hexanoic acid (HA) represent plant- and human-derived odorants, respectively, previously found as attractants for the dengue vector Aedes aegypti. Here, we investigated if a blend of both compounds can improve captures of this mosquito species in field trials in two dengue endemic sites, Kilifi and Busia Counties in Kenya. Ae. aegypti captures were significantly higher in Kilifi than Busia (χ21,142 = 170.63, P < 0.0001) and varied by treatments (χ25,137 = 151.19, P = 0.002). We found that CO2-baited BG Sentinel traps combined with a blend of both odorants decreased Ae. aegypti captures about 2- to 4-fold compared to captures with the individual compounds (LO or HA) used as positive controls. This was the case for all blends of LO and HA, irrespective of the doses tested. Our findings indicate that combining plant- and human-derived odors may elicit a masking effect in trapping Ae. aegypti. These results partly corroborate previous findings for malaria mosquitoes which showed that combining lures from both host sources either decreases or increases trap catches depending on the dose. Further investigations in the usefulness of combining plant and animal odorants in mosquito trapping are therefore necessary.