Impact of malaria control interventions on malaria infection and anaemia in low malaria transmission settings: a cross-sectional population-based study in Sudan.

BACKGROUND: The past two decades were associated with innovation and strengthening of malaria control interventions, which have been increasingly adopted at large scale. Impact evaluations of these interventions were mostly performed in moderate or high malaria transmission areas. This study aimed to evaluate the use and performance of malaria interventions in low transmission areas on malaria infections and anaemia. METHODS: Data from the 2016 Sudan malaria indicator survey was used. Multi-level logistic regression analysis was used to assess the strength of association between real-life community-level utilization of malaria interventions [diagnosis, artemisinin-based combination therapies (ACTs) and long-lasting insecticidal nets (LLINs)] and the study outcomes: malaria infections and anaemia (both overall and moderate-to-severe anaemia). RESULTS: The study analysis involved 26,469 individuals over 242 clusters. Malaria infection rate was 7.6%, overall anaemia prevalence was 47.5% and moderate-to-severe anaemia prevalence was 4.5%. The average community-level utilization was 31.5% for malaria diagnosis, 29.9% for ACTs and 35.7% for LLINs. The odds of malaria infection was significantly reduced by 14% for each 10% increase in the utilization of malaria diagnosis (adjusted odds ratio (aOR) per 10% utilization 0.86, 95% CI 0.78-0.95, p = 0.004). However, the odds of infection was positively associated with the utilization of LLINs at community-level (aOR per 10% utilization 1.20, 95% CI 1.11-1.29, p < 0.001). No association between malaria infection and utilization of ACTs was identified (aOR per 10% utilization 0.97, 95% CI 0.91-1.04, p = 0.413). None of the interventions was associated with overall anaemia nor moderate-to-severe anaemia. CONCLUSION: There was strong evidence that utilization of malaria diagnosis at the community level was highly protective against malaria infection. No protective effect was seen for community utilization of ACTs or LLINs. No association was established between any of the interventions and overall anaemia or moderate-to-severe anaemia. This lack of effectiveness could be due to the low utilization of interventions or the low level of malaria transmission in the study area. Identification and response to barriers of access and low utilization of malaria interventions are crucial. It is crucial to ensure that every suspected malaria case is tested in a timely way, notably in low transmission settings.

Impact of malaria control interventions on malaria infection and anaemia in areas with irrigated schemes: a cross-sectional population-based study in Sudan.

BACKGROUND: While the overall burden of malaria is still high, the global technical strategy for malaria advocates for two sets of interventions: vector control-based prevention and diagnosis and prompt effective treatment of malaria cases. This study aimed to assess the performance of malaria interventions on malaria infection and anaemia in irrigated areas in Sudan. METHODS: Based on the Sudan 2016 national malaria indicator survey, data for two states (Gezira and Sennar), characterized by large-irrigated schemes, were analysed. Four community-level malaria interventions were used as contextual variables: utilization of malaria diagnosis, utilization of Artemisinin-based combination therapy (ACT), utilization of long-lasting insecticidal nets (LLINs) and coverage with indoor residual spraying (IRS). Association between these interventions and two outcomes: malaria infection and anaemia, was assessed separately. Malaria infection was assessed in all age groups while anaemia was assessed in children under 5 years. Multilevel multiple logistic regression analysis were conducted. RESULTS: Among 4478 individuals involved in this study distributed over 47 clusters, the overall malaria infection rate was 3.0% and 56.5% of the children under 5 years (total = 322) were anaemic. Except for IRS coverage (69.6%), the average utilization of interventions was relatively low: 52.3% for utilization of diagnosis, 33.0% for utilization of ACTs and 18.6% for LLINs utilization. The multi-level multiple logistic regression model showed that only IRS coverage was associated with malaria infection (Odds ratio 0.83 per 10% coverage, 95%Confidence Interval (95%CI) 0.74-0.94, p = 0.003) indicating that a higher level of IRS coverage was associated with less malaria infection. Anaemia was not associated with any intervention (all p values larger than 0.1). CONCLUSIONS: Malaria transmission in Gezira and Sennar areas is low. IRS, with insecticide to which vectors are susceptible, is an effective malaria control intervention in irrigated schemes. Community utilization of other interventions was not associated with malaria infection in this study. This may be due to the low utilization of these interventions. However, individual use of LLINs provide personal protection. This study failed to establish an association between anaemia and malaria control interventions in low transmission areas. The higher level of malaria infection in urban areas is a cause for concern.

Anaemia prevalence and determinants in under 5 years children: findings of a cross-sectional population-based study in Sudan.

BACKGROUND: Early childhood is an age at risk of anaemia and its deleterious consequences. In Sudan, there is limited evidence on the prevalence and determinant of anaemia in under-five children. This study was conducted in Sudan to assess the prevalence of anaemia in children and to identify its determinants. METHODS: We conducted a household survey involving children aged 6 months to 5 years in November 2016. A representative population was sampled across rural, urban and camps settlements across 18 states in Sudan. We used a pre-designed questionnaire data collection. Haemoglobin (Hb) level and malaria infection were checked. In this cross-sectional study, we dichotomized the outcome variable and performed logistic regression analyses. RESULTS: A total of 3094 children under 5 years enrolled in the study, 1566 (50.6%) of them were female and 690 (22.3%) of them were under 2 years old. Anaemia prevalence in the whole cohort (6 months - < 5 years) was 49.4% and the mean haemoglobin concentration was 108.1 (standard deviation (SD): 15.4) g/L. The prevalence in younger (6 months - < 2 years) children (61.9%) was higher than in older (2 - < 5 years) children (45.6%) (p < 0.001). Severe anaemia (Hb < 70 g/L) prevalence in the whole population was 1.6%. Age (Odds ratio (OR) 2.25, 95% confidence interval (95%CI) 1.75-2.90, p < 0.001), type of place of residence (OR 0.37, 95%CI 0.18-0.74, p = 0.005), maternal anaemia (OR 1.74, 95%CI 1.39-2.17, p < 0.001), and malaria infection (OR 2.82, 95%CI 1.56-5.11, p < 0.001) were the identified predictors of anaemia in the whole cohort. In younger children, only the economic class was an anaemia predictor, with a lower anaemia risk among the rich wealth class (OR 2.70, 95%CI 1.29-5.62, p = 0.008). However, in older children, three anaemia predictors were identified. These are maternal anaemia (OR 1.79, 95%CI 1.40-2.28, < 0.001), malaria infection (OR 2.77, 95%CI 1.48-5.21, p = 0.002), and type of residency (where camps' residents were less likely affected with anaemia than rural children (OR 0.38, 95%CI 0.17-0.87, p = 0.022)). CONCLUSIONS: About half of the under-5 children in Sudan are anaemic, with worse prevalence in younger children. Efforts targeted at improving socio-economic status, decreasing maternal anaemia and childhood malaria infection may mitigate this alarming trend.

Prevalence and determinants of anaemia in women of reproductive age in Sudan: analysis of a cross-sectional household survey.

BACKGROUND: Anaemia is a global health problem and women in reproductive age (WRA) are amongst the most affected population. Its consequences include low birth weight and maternal mortality. This study aimed to assess the prevalence of anaemia and to identify its determinants in Sudanese women in reproductive age. METHODS: A population-based cross-sectional study was conducted in Sudan in 2016. A multi-stage stratified cluster sampling design was executed with consideration of rural population, urban population, and internally displaced persons/refugees camps residents. All women in reproductive age (15-49 years), classified by pregnancy status, in the targeted households were surveyed and personal characteristic data were collected. Their haemoglobin level and malaria infection (using rapid diagnostic test, RDT) were assessed. The World Health Organization (WHO) haemoglobin level cut-off for defining anaemia and severe anaemia in pregnant and non-pregnant women was used. Logistic regression analyses were performed. RESULTS: A total of 4271 women (WRA) of which 421 (9.9%) pregnant women (PW) were included in the study. The overall anaemia prevalence in WRA was 35.6%. It was 36.0 and 35.5% in PW and non-pregnant women (NPW), respectively. The average haemoglobin level was found to be 113.9 g/L (SD 16.3) and 123.2 g/L (SD 15.7) for PW and NPW respectively. Severe anaemia prevalence was 1.2% in each group. In the logistic regression model, anaemia was associated with malaria infection in PW (aOR 4.100, 95%CI 1.523-11.039, p = 0.003), NPW (aOR 2.776, 95%CI 1.889-4.080, p < 0.001), and WRA (aOR 2.885, 95%CI 2.021-4.119, p < 0.001). Other identified determinants of anaemia in NPW was living in camps (aOR 1.499, 95%CI 1.115-2.017, p = 0.007) and in WRA was being in the poorest economic class (aOR 1.436, 95%CI 1.065-1.936, p = 0.018). CONCLUSIONS: Anaemia is a public health problem in Sudan. The study supported the association between malaria infection and anaemia, but not with low and moderate malaria transmission areas. Resources need to be allocated for all anaemic populations with special attention for the populations in most need and interventions need to be implemented based on local variations. Malaria control interventions, specifically case management, may have a major impact in reducing anaemia prevalence in low to moderate malaria transmission areas.

Indoor residual spraying for malaria control in sub-Saharan Africa 1997 to 2017: an adjusted retrospective analysis.

BACKGROUND: Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors. To support the development of effective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecific. Here, the subnational coverage of IRS across sub-Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated. METHODS: Data on IRS deployment were collated from a variety of sources, including the President's Malaria Initiative spray reports and National Malaria Control Programme reports, for all 46 malaria-endemic countries in sub-Saharan Africa from 1997 to 2017. The data were mapped to the applicable administrative divisions and the proportion of households sprayed for each of the four main insecticide classes; carbamates, organochlorines, organophosphates and pyrethroids was calculated. RESULTS: The number of countries implementing IRS increased considerably over time, although the focal nature of deployment means the number of people protected remains low. From 1997 to 2010, DDT and pyrethroids were commonly used, then partly replaced by carbamates from 2011 and by organophosphates from 2013. IRS deployment since the publication of resistance management guidelines has typically avoided overlap between pyrethroid IRS and ITN use. However, annual rotations of insecticide classes with differing modes of action are not routinely used. CONCLUSION: This study highlights the gaps between policy and practice, emphasizing the continuing potential of IRS to drive resistance. The data presented here can improve studies on the impact of IRS on malaria incidence and help to guide future malaria control efforts.

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study.

BACKGROUND: Scale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden. METHODS: This WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis. FINDINGS: Between June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51-0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41-0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70-1·06) or incidence (adjusted RR 0·89, 0·72-1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016-0·033] per person-year in India, to 0·80 [0·65-0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5-1·3] in India to an average infection prevalence of 50·8% [43·4-58·2] in Benin). INTERPRETATION: Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden. FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

Temporal and spatial trends in insecticide resistance in Anopheles arabiensis in Sudan: outcomes from an evaluation of implications of insecticide resistance for malaria vector control.

BACKGROUND: Long-lasting insecticidal nets (LLINs) (with pyrethroids) and indoor residual spraying (IRS) are the cornerstones of the Sudanese malaria control program. Insecticide resistance to the principal insecticides in LLINs and IRS is a major concern. This study was designed to monitor insecticide resistance in Anopheles arabiensis from 140 clusters in four malaria-endemic areas of Sudan from 2011 to 2014. All clusters received LLINs, while half (n = 70), distributed across the four regions, had additional IRS campaigns. METHODS: Anopheles gambiae (s.l.) mosquitoes were identified to species level using PCR techniques. Standard WHO insecticide susceptibility bioassays were carried out to detect resistance to deltamethrin (0.05%), DDT (4%) and bendiocarb (0.1%). TaqMan assays were performed on random samples of deltamethrin-resistant phenotyped and pyrethrum spray collected individuals to determine Vgsc-1014 knockdown resistance mutations. RESULTS: Anopheles arabiensis accounted for 99.9% of any anopheline species collected across all sites. Bioassay screening indicated that mosquitoes remained susceptible to bendiocarb but were resistance to deltamethrin and DDT in all areas. There were significant increases in deltamethrin resistance over the four years, with overall mean percent mortality to deltamethrin declining from 81.0% (95% CI: 77.6-84.3%) in 2011 to 47.7% (95% CI: 43.5-51.8%) in 2014. The rate of increase in phenotypic deltamethrin-resistance was significantly slower in the LLIN + IRS arm than in the LLIN-only arm (Odds ratio 1.34; 95% CI: 1.02-1.77). The frequency of Vgsc-1014F mutation varied spatiotemporally with highest frequencies in Galabat (range 0.375-0.616) and New Halfa (range 0.241-0.447). Deltamethrin phenotypic-resistance correlated with Vgsc-1014F frequency. CONCLUSION: Combining LLIN and IRS, with different classes of insecticide, may delay pyrethroid resistance development, but the speed at which resistance develops may be area-specific. Continued monitoring is vital to ensure optimal management and control.

Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation.

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36-3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40-0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.

Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation.

BACKGROUND: Progress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper. METHODS: Malaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively. RESULTS: Cohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016. DISCUSSION: The paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design.