Exploring Barriers and Facilitators of Adherence to Artemisinin-Based Combination Therapies for the Treatment of Uncomplicated Malaria in Children in Freetown, Sierra Leone.

Medication adherence is an essential step in the malaria treatment cascade. We conducted a qualitative study embedded within a randomized controlled trial comparing the adherence to the recommended dosing of two artemisinin-based combination therapies (ACT) to treat uncomplicated malaria in Freetown, Sierra Leone. This study explored the circumstances and factors that influenced caregiver adherence to the ACT prescribed for their child in the trial. In-depth interviews were conducted with 49 caregivers; all interviews were recorded, transcribed, and translated. Transcripts were coded and aggregated into themes, applying a thematic content approach. We identified four key factors that influenced optimal treatment adherence: (1) health system influences, (2) health services, (3) caregivers' experiences with malaria illness and treatment, and (4) medication characteristics. Specifically, caregivers reported confidence in the health system as facilities were well maintained and care was free. They also felt that health workers provided quality care, leading them to trust the health workers and believe the test results. Ease of medication administration and perceived risk of side effects coupled with caregivers' prior experience treating malaria influenced how medications were administered. To ensure ACTs achieve maximum effectiveness, consideration of these contextual factors and further development of child-friendly antimalarials are needed.

Molecular Detection of Insecticide Resistance Mutations in Anopheles gambiae from Sierra Leone Using Multiplex SNaPshot and Sequencing.

Vector control interventions including long-lasting insecticidal nets and indoor residual spraying are important for malaria control and elimination. And effectiveness of these interventions depends entirely on the high level of susceptibility of malaria vectors to insecticides. However, the insecticide resistance in majority of mosquito vector species across African countries is a serious threat to the success of vector control efforts with the extensive use of insecticides, while no data on insecticide resistance was reported from Sierra Leone in the past decade. In the present study, the polymerase chain reaction was applied for the identification of species of 757 dry adult female Anopheles gambiae mosquitoes reared from larvae collected from four districts in Sierra Leone during May and June 2018. And the mutations of kdr, rdl, ace-1 genes in An. gambiae were detected using SNaPshot and sequencing. As a result, one sample from Western Area Rural district belonged to Anopheles melas, and 748 An. gambiae were identified. Furthermore, the rdl mutations, kdr west mutations and ace-1 mutation were found. The overall frequency was 35.7%, 0.3%, 97.6% and 4.5% in A296G rdl, A296S rdl, kdrW and ace-1, respectively. The frequencies of A296G rdl mutation (P < 0.001), kdrW mutation (P = 0.001) and ace-1 mutation (P < 0.001) were unevenly distributed in four districts, respectively, while no statistical significance was found in A296S rdl mutation (P = 0.868). In addition, multiple resistance patterns were also found. In conclusion, multiple mutations involved in insecticide resistance in An. gambiae populations in Sierra Leone were detected in the kdrW, A296G rdl and ace-1 alleles in the present study. It is necessary to monitor vector susceptibility levels to insecticides used in this country, and update the insecticide resistance monitoring and management strategy.

Screening, Vaccination Uptake and Linkage to Care for Hepatitis B Virus among Health Care Workers in Rural Sierra Leone.

This study reports on the prevalence and risk factors of chronic HBV among health care workers (HCWs) in a rural secondary hospital in Sierra Leone. Additionally, data on the uptake of HBV vaccination among negatively tested HCWs and on the linkage to care among positively tested HCWs are presented. In December 2019, 781 HCWs were invited to a screening and vaccination campaign at Koidu Government Hospital in Kono District. For each HCW, demographic information and data on their HBV risk history were captured, followed by a hepatitis B surface antigen (HBsAg) test. HCWs with a negative test result were offered an HBV vaccine on the same day, after one and six months. HCWs that were HBsAg positive were linked to a free HBV clinic. In total, 80% (632) of HCWs were screened. Among the screened, 97% had never received an HBV vaccine and 10.3% (n = 65) had chronic HBV. The following characteristics were associated with being HBsAg positive: aged less than 30 years old (aOR 2.17, CI 1.16-4.03, p = 0.01), male gender (aOR 2.0, CI 1.06-3.78, p = 0.03), working experience of 1-4 years (aOR 3.99, CI 1.15-13.73, p = 0.03) and over 9 years (aOR 6.16, CI 1.41-26.9, p = 0.02). For HBsAg-negative HCWs (n = 567), 99.8% (n = 566), 97.5% (n = 553) and 82.7% (n = 469) received their first, second and third dose of the vaccine, respectively. For HBsAg-positive HCWs (n = 65), 73.9% (n = 48) were successfully linked to an HBV clinic for further care. Most HCWs are unvaccinated for HBV, and the HBV prevalence amongst this at-risk group is high. Uptake of vaccination and linkage to care was successful.

A Household-Based Cross-Sectional Survey of Knowledge, Awareness and Practice Regarding Malaria in Western Area Rural District, Sierra Leone.

Sierra Leone is a highly endemic area for malaria, and the implementation of the National Malaria Strategic Plan (2016-2020) has reached its midpoint in 2018. To provide more specific guidance for interventions in the future, a household-based cross-sectional survey was conducted to elucidate the knowledge, awareness and practices regarding malaria and malarial control measures among the general public. Three communities (Grafton, Jui, and Kossoh) in the Western Area Rural District that were in close proximity to Sierra Leone's capital city of Freetown were included. Households were randomly selected and interviewed with a structured questionnaire covering malaria infection, diagnosis, treatment and prevention, as well as knowledge of malaria prevention. As a result, a total of 262 qualified questionnaires were included. The average cost for meals per day is ~30,000 Leones in each household. The rate of awareness, indicated by reporting having heard of malaria, was 98.1% (257/262), and 86.6% (227/262) of the respondents knew that mosquito bites are the main route of transmission. In addition, 80.9% (212/262) of the respondents sought health advice or treatment for the illness, and a similar percentage of respondents had been tested for malaria, mostly with rapid diagnostic tests (RDTs). A high demand for long-lasting insecticidal nets (72.1%) matched the serious shortage (61.8%, 162/262), and of the households that reported a lack of nets, 66 had children younger than 5 years old. In conclusion, public awareness of malaria prevention is high, based on this survey, although there was a limited use of preventive measures in these three communities and the malaria burden was still high. Therefore, the public's knowledge of malaria should be sustained and reinforced, and the distribution and use of malaria prevention measures should be promoted to supprt the achievement of the planned objectives.

First report of N1575Y mutation in Anopheles gambiae in Sierra Leone.

The resistance of mosquito vectors to insecticides is one of the biological obstacles in the fight against malaria. Understanding of the status and mechanisms underlying the insecticide resistance in Anopheles gambiae species is necessary for success of vector control efforts. The study aimed to determine the molecular forms of An. gambiae from four districts in Sierra Leone during May and June 2018, and the level of N1575Y mutation. The molecular form identification of adult female An. gambiae mosquitoes reared from larvae were carried out using polymerase chain reaction and sequencing. And the N1575Y mutations were detected using SNaPshot and sequencing. As a result, significant differences were found in the distribution of An. gambiae molecular forms among regions (P < 0.001). And a total of 638 An. gambiae sensu stricto, 106 An. coluzzi, and 4 hybrid individuals were identified. Moreover, the overall N1575Y mutation frequency was 10.2% with no statistical difference among regions (χ2 = 3.009, P = 0.390). In addition, no significant differences in N1575Y mutation frequency were found among different An. gambiae molecular forms (P = 0.383). In conclusion, the N1575Y mutation in An. gambiae populations in Sierra Leone was reported for the first time in the present study. It provides key evidence for the necessity of monitoring vector susceptibility levels to insecticides used in this country.

Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone.

BACKGROUND: Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. METHODS: This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15-17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3-15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. RESULTS: Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2-7%]; 11% post-IPTi [95%CI 8-15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. CONCLUSIONS: Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

Factors associated with access and adherence to artemisinin-based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone.

BACKGROUND: Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five. METHODS: The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression. RESULTS: Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02-3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29-2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27-2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20-4.44; p = 0.025), and age (24-59 vs. 0-23 months; OR 1.45, 95% CI 1.07-1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34-0.89; p = 0.015). CONCLUSIONS: In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.

Adherence to treatment with artemether-lumefantrine or amodiaquine-artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial.

BACKGROUND: Prompt, effective treatment of confirmed malaria cases with artemisinin-based combination therapy (ACT) is a cornerstone of malaria control. Maximizing adherence to ACT medicines is key to ensuring treatment effectiveness. METHODS: This open-label, randomized trial evaluated caregiver adherence to co-formulated artemether-lumefantrine (AL) and fixed-dose amodiaquine-artesunate (AQAS) in Sierra Leone. Children aged 6-59 months diagnosed with malaria were recruited from two public clinics, randomized to receive AL or AQAS, and visited at home the day after completing treatment. Analyses were stratified by site, due to differences in participant characteristics and outcomes. RESULTS: Of the 784 randomized children, 680 (85.6%) were included in the final per-protocol analysis (340 AL, 340 AQAS). Definite adherence (self-reported adherence plus empty package) was higher for AL than AQAS at both sites (Site 1: 79.4% AL vs 63.4% AQAS, odds ratio [OR] 2.16, compared to probable adherence plus probable or definite non-adherence, 95% confidence interval [CI] 1.34-3.49; p = 0.001; Site 2: 52.1% AL vs 37.5% AQAS, OR 1.53, 95% CI 1.00-2.33, p = 0.049). However, self-reported adherence (ignoring drug package inspection) was higher for both regimens at both sites and there was no strong evidence of variation by treatment (Site 1: 96.6% AL vs 95.9% AQAS, OR 1.19, 95% CI 0.39-3.63, p = 0.753; Site 2: 91.5% AL vs 96.4% AQAS, OR 0.40, 95% CI 0.15-1.07, p = 0.067). In Site 2, correct treatment (correct dose + timing + duration) was lower for AL than AQAS (75.8% vs 88.1%, OR 0.42, 95% CI 0.23-0.76, p = 0.004). In both sites, more caregivers in the AQAS arm reported adverse events (Site 1: 3.4% AL vs 15.7% AQAS, p < 0.001; Site 2: 15.2% AL vs 24.4% AQAS, p = 0.039). CONCLUSIONS: Self-reported adherence was high for both AL and AQAS, but varied by site. These results suggest that each regimen has potential disadvantages that might affect adherence; AL was less likely to be taken correctly at one site, but was better tolerated than AQAS at both sites. Measuring adherence to anti-malarials remains challenging, but important. Future research should focus on comparative studies of new drug regimens, and improving the methodology of measuring adherence. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01967472. Retrospectively registered 18 October 2013, https://clinicaltrials.gov/ct2/show/NCT01967472.

Household possession and use of insecticide-treated mosquito nets in Sierra Leone 6 months after a national mass-distribution campaign.

BACKGROUND: In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. METHODS: We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. RESULTS: The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥ 1:2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥ 1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. CONCLUSIONS: The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.