Private sector role, readiness and performance for malaria case management in Uganda, 2015

Abstract Background Several interventions have been put in place to promote access to quality malaria case management services in Uganda’s private sector, where most people seek treatment. This paper describes evidence using a mixed-method approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector. Methods The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 and July 2nd 2015. A representative sample of sub-counties was selected in 14 urban and 13 rural clusters with probability proportional to size and a census approach was used to identify outlets. Outlets eligible for the survey met at least one of three criteria: (1) one or more anti-malarials were in stock on the day of the survey; (2) one or more anti-malarials were in stock in the 3 months preceding the survey; and/or (3) malaria blood testing (microscopy or RDT) was available. The fever case management study included observations of provider-patient interactions and patient exit interviews. Data were collected between May 20th and August 3rd, 2015. The fever case management study was implemented in the private sector. Potential outlets were identified during the main outlet survey and included in this sub-sample if they had both artemisinin-based combination therapy (ACT) [artemether–lumefantrine (AL)], in stock on the day of survey as well as diagnostic testing available. Results A total of 9438 outlets were screened for eligibility in the ACTwatch outlet survey and 4328 outlets were found to be stocking anti-malarials and were interviewed. A total of 9330 patients were screened for the fever case management study and 1273 had a complete patient observation and exit interview. Results from the outlet survey illustrate that the majority of anti-malarials were distributed through the private sector (54.3%), with 31.4% of all anti-malarials distributed through drug stores and 14.4% through private for-profit health facilities. Availability of different anti-malarials and diagnostic testing in the private sector was: ACT (80.7%), quality-assured (QA) ACT (72.0%), sulfadoxine–pyrimethamine (SP) (47.1%), quinine (73.2%) and any malaria blood testing (32.9%). Adult QAACT ($1.62) was three times more expensive than SP ($0.48). The results from the fever case management study found 44.4% of respondents received a malaria test, and among those who tested positive for malaria, 60.0% received an ACT, 48.5% received QAACT; 14.4% a non-artemisinin therapy; 14.9% artemether injection, and 42.5% received an antibiotic. Conclusion The private sector plays an important role in malaria case management in Uganda. While several private sector initiatives have improved availability of QAACT, there are gaps in malaria diagnosis and distribution of non-artemisinin monotherapies persists. Further private sector strategies, including those focusing on drug stores, are needed to increase coverage of parasitological testing and removal of non-artemisinin therapies from the marketplace

Private sector role, readiness and performance for malaria case management in Uganda, 2015.

BACKGROUND: Several interventions have been put in place to promote access to quality malaria case management services in Uganda\u27s private sector, where most people seek treatment. This paper describes evidence using a mixed-method approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector. METHODS: The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 and July 2nd 2015. A representative sample of sub-counties was selected in 14 urban and 13 rural clusters with probability proportional to size and a census approach was used to identify outlets. Outlets eligible for the survey met at least one of three criteria: (1) one or more anti-malarials were in stock on the day of the survey; (2) one or more anti-malarials were in stock in the 3 months preceding the survey; and/or (3) malaria blood testing (microscopy or RDT) was available. The fever case management study included observations of provider-patient interactions and patient exit interviews. Data were collected between May 20th and August 3rd, 2015. The fever case management study was implemented in the private sector. Potential outlets were identified during the main outlet survey and included in this sub-sample if they had both artemisinin-based combination therapy (ACT) [artemether-lumefantrine (AL)], in stock on the day of survey as well as diagnostic testing available. RESULTS: A total of 9438 outlets were screened for eligibility in the ACTwatch outlet survey and 4328 outlets were found to be stocking anti-malarials and were interviewed. A total of 9330 patients were screened for the fever case management study and 1273 had a complete patient observation and exit interview. Results from the outlet survey illustrate that the majority of anti-malarials were distributed through the private sector (54.3%), with 31.4% of all anti-malarials distributed through drug stores and 14.4% through private for-profit health facilities. Availability of different anti-malarials and diagnostic testing in the private sector was: ACT (80.7%), quality-assured (QA) ACT (72.0%), sulfadoxine-pyrimethamine (SP) (47.1%), quinine (73.2%) and any malaria blood testing (32.9%). Adult QAACT ($1.62) was three times more expensive than SP ($0.48). The results from the fever case management study found 44.4% of respondents received a malaria test, and among those who tested positive for malaria, 60.0% received an ACT, 48.5% received QAACT; 14.4% a non-artemisinin therapy; 14.9% artemether injection, and 42.5% received an antibiotic. CONCLUSION: The private sector plays an important role in malaria case management in Uganda. While several private sector initiatives have improved availability of QAACT, there are gaps in malaria diagnosis and distribution of non-artemisinin monotherapies persists. Further private sector strategies, including those focusing on drug stores, are needed to increase coverage of parasitological testing and removal of non-artemisinin therapies from the marketplace

Measuring health facility readiness and its effects on severe malaria outcomes in Uganda

There is paucity of evidence for the role of health service delivery to the malaria decline in Uganda We developed a methodology to quantify health facility readiness and assessed its role on severe malaria outcomes among lower-level facilities (HCIIIs and HCIIs) in the country. Malaria data was extracted from the Health Management Information System (HMIS). General service and malaria-specific readiness indicators were obtained from the 2013 Uganda service delivery indicator survey. Multiple correspondence analysis (MCA) was used to construct a composite facility readiness score based on multiple factorial axes. Geostatistical models assessed the effect of facility readiness on malaria deaths and severe cases. Malaria readiness was achieved in one-quarter of the facilities. The composite readiness score explained 48% and 46% of the variation in the original indicators compared to 23% and 27%, explained by the first axis alone for HCIIIs and HCIIs, respectively. Mortality rate was 64% (IRR = 0.36, 95% BCI: 0.14-0.61) and 68% (IRR = 0.32, 95% BCI: 0.12-0.54) lower in the medium and high compared to low readiness groups, respectively. A composite readiness index is more informative and consistent than the one based on the first MCA factorial axis. In Uganda, higher facility readiness is associated with a reduced risk of severe malaria outcomes

The effect of case management and vector-control interventions on space-time patterns of malaria incidence in Uganda

Electronic reporting of routine health facility data in Uganda began with the adoption of the District Health Information Software System version 2 (DHIS2) in 2011. This has improved health facility reporting and overall data quality. In this study, the effects of case management with artemisinin-based combination therapy (ACT) and vector control interventions on space-time patterns of disease incidence were determined using DHIS2 data reported during 2013-2016.; Bayesian spatio-temporal negative binomial models were fitted on district-aggregated monthly malaria cases, reported by two age groups, defined by a cut-off age of 5 years. The effects of interventions were adjusted for socio-economic and climatic factors. Spatial and temporal correlations were taken into account by assuming a conditional autoregressive and a first-order autoregressive AR(1) process on district and monthly specific random effects, respectively. Fourier trigonometric functions were incorporated in the models to take into account seasonal fluctuations in malaria transmission.; The temporal variation in incidence was similar in both age groups and depicted a steady decline up to February 2014, followed by an increase from March 2015 onwards. The trends were characterized by a strong bi-annual seasonal pattern with two peaks during May-July and September-December. Average monthly incidence in children < 5 years declined from 74.7 cases (95% CI 72.4-77.1) in 2013 to 49.4 (95% CI 42.9-55.8) per 1000 in 2015 and followed by an increase in 2016 of up to 51.3 (95% CI 42.9-55.8). In individuals ≥ 5 years, a decline in incidence from 2013 to 2015 was followed by an increase in 2016. A 100% increase in insecticide-treated nets (ITN) coverage was associated with a decline in incidence by 44% (95% BCI 28-59%). Similarly, a 100% increase in ACT coverage reduces incidence by 28% (95% BCI 11-45%) and 25% (95% BCI 20-28%) in children < 5 years and individuals ≥ 5 years, respectively. The ITN effect was not statistically important in older individuals. The space-time patterns of malaria incidence in children < 5 are similar to those of parasitaemia risk predicted from the malaria indicator survey of 2014-15.; The decline in malaria incidence highlights the effectiveness of vector-control interventions and case management with ACT in Uganda. This calls for optimizing and sustaining interventions to achieve universal coverage and curb reverses in malaria decline

The age-specific incidence of hospitalized paediatric malaria in Uganda.

BACKGROUND: Understanding the relationship between malaria infection risk and disease outcomes represents a fundamental component of morbidity and mortality burden estimations. Contemporary data on severe malaria risks among populations of different parasite exposures are scarce. Using surveillance data, we compared rates of paediatric malaria hospitalisation in areas of varying parasite exposure levels. METHODS: Surveillance data at five public hospitals; Jinja, Mubende, Kabale, Tororo, and Apac were assembled among admissions aged 1 month to 14 years between 2017 and 2018. The address of each admission was used to define a local catchment population where national census data was used to define person-year-exposure to risk. Within each catchment, historical infection prevalence was assembled from previously published data and current infection prevalence defined using 33 population-based school surveys among 3400 children. Poisson regression was used to compute the overall and site-specific incidences with 95% confidence intervals. RESULTS: Both current and historical Plasmodium falciparum prevalence varied across the five sites. Current prevalence ranged from < 1% in Kabale to 54% in Apac. Overall, the malaria admission incidence rate (IR) was 7.3 per 1000 person years among children aged 1 month to 14 years of age (95% CI: 7.0, 7.7). The lowest rate was described at Kabale (IR = 0.3; 95 CI: 0.1, 0.6) and highest at Apac (IR = 20.3; 95 CI: 18.9, 21.8). There was a correlation between IR across the five sites and the current parasite prevalence in school children, though findings were not statistically significant. Across all sites, except Kabale, malaria admissions were concentrated among young children, 74% were under 5 years. The median age of malaria admissions at Kabale hospital was 40 months (IQR 20, 72), and at Apac hospital was 36 months (IQR 18, 69). Overall, severe anaemia (7.6%) was the most common presentation and unconsciousness (1.8%) the least common. CONCLUSION: Malaria hospitalisation rates remain high in Uganda particularly among young children. The incidence of hospitalized malaria in different locations in Uganda appears to be influenced by past parasite exposure, immune acquisition, and current risks of infection. Interruption of transmission through vector control could influence age-specific severe malaria risk

LLIN Evaluation in Uganda Project (LLINEUP) - Impact of long-lasting insecticidal nets with, and without, piperonyl butoxide on malaria indicators in Uganda: study protocol for a cluster-randomised trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are a key malaria control intervention, but their effectiveness is threatened by resistance to pyrethroid insecticides. Some new LLINs combine pyrethroids with piperonyl butoxide (PBO), a synergist that can overcome P450-based metabolic resistance to pyrethroids in mosquitoes. In 2017-2018, the Ugandan Ministry of Health distributed LLINs with and without PBO through a national mass-distribution campaign, providing a unique opportunity to rigorously evaluate PBO LLINs across different epidemiological settings. METHODS/DESIGN: Together with the Ministry of Health, we embedded a cluster-randomised trial to evaluate the impact of LLINs delivered in the 2017-2018 national campaign. A total of 104 clusters (health sub-districts) in Eastern and Western Uganda were involved, covering 48 of 121 (40%) districts. Using adaptive randomisation driven by the number of LLINs available, clusters were assigned to receive one of four types of LLINs, including two brands with PBO: 1) PermaNet 3.0 (n = 32) and 2) Olyset Plus (n = 20); and two without PBO: 3) PermaNet 2.0 (n = 37) and 4) Olyset Net (n = 15). We are conducting cross-sectional community surveys in 50 randomly selected households per cluster (5200 households per survey) and entomological surveillance for insecticide resistance in up to 10 randomly selected households enrolled in the community surveys per cluster (1040 households per survey) at baseline and 6, 12, and 18 months after LLIN distribution. Net durability and bio-efficacy will be assessed in 400 nets withdrawn from households with replacement at 12 months. The primary trial outcome is parasite prevalence as measured by microscopy in children aged 2-10 years in the follow-up surveys. DISCUSSION: PBO LLINs are a promising new tool to reduce the impact of pyrethroid resistance on malaria control. The World Health Organization has issued a preliminary endorsement of PBO LLINs, but additional epidemiological evidence of the effect of PBO LLINs is urgently needed. The results of this innovative, large-scale trial embedded within a routine national distribution campaign will make an important contribution to the malaria control policy in Uganda and throughout Africa, where pyrethroid resistance in malaria vectors has increased dramatically. This model of evaluation could be a paradigm for future assessment of malaria control interventions. TRIAL REGISTRATION: ISRCTN, ISRCTN17516395 . Registered on 14 February 2017. WORLD HEALTH ORGANIZATION TRIAL REGISTRATION DATA SET: See Additional file 1

Spatial-temporal patterns of malaria incidence in Uganda using HMIS data from 2015 to 2019.

BACKGROUND: As global progress to reduce malaria transmission continues, it is increasingly important to track changes in malaria incidence rather than prevalence. Risk estimates for Africa have largely underutilized available health management information systems (HMIS) data to monitor trends. This study uses national HMIS data, together with environmental and geographical data, to assess spatial-temporal patterns of malaria incidence at facility catchment level in Uganda, over a recent 5-year period. METHODS: Data reported by 3446 health facilities in Uganda, between July 2015 and September 2019, was analysed. To assess the geographic accessibility of the health facilities network, AccessMod was employed to determine a three-hour cost-distance catchment around each facility. Using confirmed malaria cases and total catchment population by facility, an ecological Bayesian conditional autoregressive spatial-temporal Poisson model was fitted to generate monthly posterior incidence rate estimates, adjusted for caregiver education, rainfall, land surface temperature, night-time light (an indicator of urbanicity), and vegetation index. RESULTS: An estimated 38.8 million (95% Credible Interval [CI]: 37.9-40.9) confirmed cases of malaria occurred over the period, with a national mean monthly incidence rate of 20.4 (95% CI: 19.9-21.5) cases per 1000, ranging from 8.9 (95% CI: 8.7-9.4) to 36.6 (95% CI: 35.7-38.5) across the study period. Strong seasonality was observed, with June-July experiencing highest peaks and February-March the lowest peaks. There was also considerable geographic heterogeneity in incidence, with health facility catchment relative risk during peak transmission months ranging from 0 to 50.5 (95% CI: 49.0-50.8) times higher than national average. Both districts and health facility catchments showed significant positive spatial autocorrelation; health facility catchments had global Moran's I = 0.3 (p < 0.001) and districts Moran's I = 0.4 (p < 0.001). Notably, significant clusters of high-risk health facility catchments were concentrated in Acholi, West Nile, Karamoja, and East Central - Busoga regions. CONCLUSION: Findings showed clear countrywide spatial-temporal patterns with clustering of malaria risk across districts and health facility catchments within high risk regions, which can facilitate targeting of interventions to those areas at highest risk. Moreover, despite high and perennial transmission, seasonality for malaria incidence highlights the potential for optimal and timely implementation of targeted interventions

Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda.

BACKGROUND: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. METHODS: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. RESULTS: Overall, 896,550 patient visits were included in the study; 211,632 aged  15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in  15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. CONCLUSIONS: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies

LLIN Evaluation in Uganda Project (LLINEUP): factors associated with childhood parasitaemia and anaemia 3 years after a national long-lasting insecticidal net distribution campaign: a cross-sectional survey.

BACKGROUND: Recent reductions in malaria burden have been attributed largely to long-lasting insecticidal nets (LLINs). In March-June 2017, approximately 3 years after a national LLIN distribution campaign, a cross-sectional community survey was conducted to investigate factors associated with malaria parasitaemia and anaemia, in advance of Uganda's 2017-2018 LLIN campaign. METHODS: Households from 104 clusters in 48 districts were randomly selected using two-staged cluster sampling; 50 households were enrolled per cluster. Eligible children aged 2-10 years had blood obtained for a thick blood smear and those aged 2-4 years had haemoglobin measured. Associations between outcomes and variables of interest were assessed using log-binomial regression with generalized estimating equations to adjust for household clustering. RESULTS: In total, 5196 households, 8834 children with blood smear results, and 3753 with haemoglobin results were included. Only 16% of children lived in households with adequate LLIN coverage. Overall, parasite prevalence was 26.0%, ranging from 8.0% in the South West to 53.1% in East Central. Limiting data to children 2-4 years of age, parasite prevalence was 21.4%, up from 16.9% in 2014-2015 following the national LLIN campaign. In a multivariate analysis, factors associated with parasitaemia included region (East-Central vs South-Western; adjusted prevalence ratio [aPR] 6.45, 95% CI 5.55-7.50; p < 0.001), older age (8-10 vs 2-3 years; aPR 1.57, 95% CI 1.43-1.72; p < 0.001), living in a poorer household (poorest vs least poor tercile; aPR 2.32, 95% CI 2.05-2.63; p < 0.001), one constructed of traditional materials (aPR 1.13, 95% CI 1.03-1.24; p = 0.008), or without adequate LLIN coverage (aPR 1.30, 95% CI 1.14-1.48; p < 0.001). Overall, the prevalence of anaemia (haemoglobin < 10 g/dL) was 15.1% and varied geographically. In a multivariate analysis, factors associated with anaemia included region, younger age, living in a traditional house, and parasitaemia, which was the strongest predictor (aPR 2.50, 95% CI 2.12-2.95; p < 0.001). CONCLUSIONS: Three years after a national LLIN campaign, LLIN coverage was low and parasite prevalence had increased. Parasite prevalence varied widely across Uganda; older children, those living in poorer households, and those with inadequate LLIN coverage, were at highest risk of parasitaemia. LLINs may need to be distributed more frequently through mass campaigns or continuously through sustainable mechanisms. Targeting interventions to geographic areas and populations at highest risk should also be considered

LLIN evaluation in Uganda project (LLINEUP2): association between housing construction and malaria burden in 32 districts

Background: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts. Methods: Houses were classified as ‘improved’ (synthetic walls and roofs, eaves closed or absent) or ‘less-improved’ (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression. Results: Between November 2021 and March 2022, 4.893 children aged 2–10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33–0.53, p 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19–0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36–0.44, p < 0.0001) compared to communities with < 39% of houses improved. Conclusions: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control