Publications by authors named "Jimmy Opigo"

25 Publications

  • Page 1 of 1

The impact of stopping and starting indoor residual spraying on malaria burden in Uganda.

Nat Commun 2021 05 11;12(1):2635. Epub 2021 May 11.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

The scale-up of malaria control efforts has led to marked reductions in malaria burden over the past twenty years, but progress has slowed. Implementation of indoor residual spraying (IRS) of insecticide, a proven vector control intervention, has been limited and difficult to sustain partly because questions remain on its added impact over widely accepted interventions such as bed nets. Using data from 14 enhanced surveillance health facilities in Uganda, a country with high bed net coverage yet high malaria burden, we estimate the impact of starting and stopping IRS on changes in malaria incidence. We show that stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months, but reinstating IRS was associated with an over 5-fold decrease within 8 months. In areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4. IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.
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http://dx.doi.org/10.1038/s41467-021-22896-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113470PMC
May 2021

Trends in access to anti-malarial treatment in the formal private sector in Uganda: an assessment of availability and affordability of first-line anti-malarials and diagnostics between 2007 and 2018.

Malar J 2021 Mar 10;20(1):142. Epub 2021 Mar 10.

Utrecht Centre for Pharmaceutical Policy and Regulation, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.

Background: Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018.

Methods: Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days' wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria.

Results: Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day's wages for LPGW.

Conclusions: Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme.
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http://dx.doi.org/10.1186/s12936-021-03680-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944888PMC
March 2021

Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

PLoS One 2020 31;15(12):e0244457. Epub 2020 Dec 31.

College of Health Sciences, Makerere University, Kampala, Uganda.

Background: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings.

Methods: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results.

Results: The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/μl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62-4.38, P = 0.001; aOR 4.4, 95% CI 1.72-13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3-38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/μl).

Conclusion: This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244457PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774953PMC
March 2021

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

BMC Public Health 2020 Dec 14;20(1):1913. Epub 2020 Dec 14.

Department of Disease Control, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

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.
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http://dx.doi.org/10.1186/s12889-020-10007-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737387PMC
December 2020

Changing malaria fever test positivity among paediatric admissions to Tororo district hospital, Uganda 2012-2019.

Malar J 2020 Nov 19;19(1):416. Epub 2020 Nov 19.

Population Health Unit, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya.

Background: The World Health Organization (WHO) promotes long-lasting insecticidal nets (LLIN) and indoor residual house-spraying (IRS) for malaria control in endemic countries. However, long-term impact data of vector control interventions is rarely measured empirically.

Methods: Surveillance data was collected from paediatric admissions at Tororo district hospital for the period January 2012 to December 2019, during which LLIN and IRS campaigns were implemented in the district. Malaria test positivity rate (TPR) among febrile admissions aged 1 month to 14 years was aggregated at baseline and three intervention periods (first LLIN campaign; Bendiocarb IRS; and Actellic IRS + second LLIN campaign) and compared using before-and-after analysis. Interrupted time-series analysis (ITSA) was used to determine the effect of IRS (Bendiocarb + Actellic) with the second LLIN campaign on monthly TPR compared to the combined baseline and first LLIN campaign periods controlling for age, rainfall, type of malaria test performed. The mean and median ages were examined between intervention intervals and as trend since January 2012.

Results: Among 28,049 febrile admissions between January 2012 and December 2019, TPR decreased from 60% at baseline (January 2012-October 2013) to 31% during the final period of Actellic IRS and LLIN (June 2016-December 2019). Comparing intervention intervals to the baseline TPR (60.3%), TPR was higher during the first LLIN period (67.3%, difference 7.0%; 95% CI 5.2%, 8.8%, p < 0.001), and lower during the Bendiocarb IRS (43.5%, difference - 16.8%; 95% CI - 18.7%, - 14.9%) and Actellic IRS (31.3%, difference - 29.0%; 95% CI - 30.3%, - 27.6%, p < 0.001) periods. ITSA confirmed a significant decrease in the level and trend of TPR during the IRS (Bendicarb + Actellic) with the second LLIN period compared to the pre-IRS (baseline + first LLIN) period. The age of children with positive test results significantly increased with time from a mean of 24 months at baseline to 39 months during the final IRS and LLIN period.

Conclusion: IRS can have a dramatic impact on hospital paediatric admissions harbouring malaria infection. The sustained expansion of effective vector control leads to an increase in the age of malaria positive febrile paediatric admissions. However, despite large reductions, malaria test-positive admissions continued to be concentrated in children aged under five years. Despite high coverage of IRS and LLIN, these vector control measures failed to interrupt transmission in Tororo district. Using simple, cost-effective hospital surveillance, it is possible to monitor the public health impacts of IRS in combination with LLIN.
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http://dx.doi.org/10.1186/s12936-020-03490-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678291PMC
November 2020

Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017-2019.

Malar J 2020 Aug 26;19(1):300. Epub 2020 Aug 26.

QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Background: Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda.

Methods: Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR.

Results: Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6-13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4-5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7-20.0%) compared to the western region 3.1% (95% CI 0.8-7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02-23.55), p = 0.003.

Conclusions: This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.
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http://dx.doi.org/10.1186/s12936-020-03362-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449024PMC
August 2020

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

BMC Infect Dis 2020 Jul 13;20(1):503. Epub 2020 Jul 13.

Population Health Unit, Kenya Medical Research Institute/Wellcome Trust Research Programme, Nairobi, Kenya.

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.
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http://dx.doi.org/10.1186/s12879-020-05215-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359223PMC
July 2020

Malaria Outbreak Facilitated by Appearance of Vector-Breeding Sites after Heavy Rainfall and Inadequate Preventive Measures: Nwoya District, Northern Uganda, February-May 2018.

J Environ Public Health 2020 22;2020:5802401. Epub 2020 Apr 22.

Uganda Public Health Fellowship Program, Ministry of Health, Kampala, Uganda.

Background: Malaria is a leading cause of morbidity and mortality in Uganda. In April 2018, malaria cases surged in Nwoya District, Northern Uganda, exceeding expected limits and thereby requiring epidemic response. We investigated this outbreak to estimate its magnitude, identify exposure factors for transmission, and recommend evidence-based control measures.

Methods: We defined a malaria case as onset of fever in a resident of Anaka subcounty, Koch Goma subcounty, and Nwoya Town Council, Nwoya District, with a positive rapid diagnostic test or microscopy for malaria from 1 February to 25 May 2018. We reviewed medical records in all health facilities of affected subcounties to find cases. In a case-control study, we compared exposure factors between case-persons and asymptomatic controls matched by age and village. We also conducted entomological assessments on vector density and behavior.

Results: We identified 3,879 case-persons (attack rate [AR] = 6.5%) and two deaths (case-fatality rate = 5.2/10,000). Females (AR = 8.1%) were more affected than males (AR = 4.7%) ( < 0.0001). Of all age groups, 5-18 years (AR = 8.4%) were most affected. Heavy rain started in early March 2018, and a propagated outbreak followed in the first week of April 2018. In the case-control study, 55% (59/107) of case-persons and 18% (19/107) of controls had stagnant water around households for several days following rainfall (OR = 5.6, 95% CI = 3.0-11); 25% (27/107) of case-persons and 51% (55/107) of controls wore full extremity covering clothes during evening hours (OR = 0.30, 95% CI = 0.20-0.60); 71% (76/107) of case-persons and 85% (91/107) of controls slept under a long-lasting insecticide-treated net (LLIN) 14 days before symptom onset (OR = 0.43, 95% CI = 0.22-0.85); 37% (40/107) of case-persons and 52% (56/107) of controls had access to at least one LLIN per 2 household members (OR = 0.54, 95% CI = 0.30-0.97). Entomological assessment indicated active breeding sites in the entire study area; species were the predominant vector.

Conclusion: Increased vector-breeding sites after heavy rainfall and inadequate malaria preventive measures were found to have contributed to this outbreak. We recommended increasing coverage for LLINs and larviciding breeding sites in the area.
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http://dx.doi.org/10.1155/2020/5802401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193302PMC
October 2020

Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign.

Lancet 2020 04;395(10232):1292-1303

Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK; Wellcome Sanger Institute, Hinxton, UK.

Background: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention tool, but their effectiveness is threatened by pyrethroid resistance. We embedded a pragmatic cluster-randomised trial into Uganda's national LLIN campaign to compare conventional LLINs with those containing piperonyl butoxide (PBO), a synergist that can partially restore pyrethroid susceptibility in mosquito vectors.

Methods: 104 health sub-districts, from 48 districts in Uganda, were randomly assigned to LLINs with PBO (PermaNet 3.0 and Olyset Plus) and conventional LLINs (PermaNet 2.0 and Olyset Net) by proportionate randomisation using an iterative process. At baseline 6, 12, and 18 months after LLIN distribution, cross-sectional surveys were done in 50 randomly selected households per cluster (5200 per survey); a subset of ten households per cluster (1040 per survey) were randomly selected for entomological surveys. The primary outcome was parasite prevalence by microscopy in children aged 2-10 years, assessed in the as-treated population at 6, 12, and 18 months. This trial is registered with ISRCTN, ISRCTN17516395.

Findings: LLINs were delivered to households from March 25, 2017, to March 18, 2018, 32 clusters were randomly assigned to PermaNet 3.0, 20 to Olyset Plus, 37 to PermaNet 2.0, and 15 to Olyset Net. In the as-treated analysis, three clusters were excluded because no dominant LLIN was received, and four clusters were reassigned, resulting in 49 PBO LLIN clusters (31 received PermaNet 3.0 and 18 received Olyset Plus) and 52 non-PBO LLIN clusters (39 received PermaNet 2.0 and 13 received Olyset Net). At 6 months, parasite prevalence was 11% (386/3614) in the PBO group compared with 15% (556/3844) in the non-PBO group (prevalence ratio [PR] adjusted for baseline values 0·74, 95% CI 0·62-0·87; p=0·0003). Parasite prevalence was similar at month 12 (11% vs 13%; PR 0·73, 95% CI 0·63-0·85; p=0·0001) and month 18 (12% vs 14%; PR 0·84, 95% CI 0·72-0·98; p=0·029).

Interpretation: In Uganda, where pyrethroid resistance is high, PBO LLINs reduced parasite prevalence more effectively than did conventional LLINs for up to 18 months. This study provides evidence needed to support WHO's final recommendation on use of PBO LLINs.

Funding: The Against Malaria Foundation, UK Department for International Development, Innovative Vector Control Consortium, and Bill and Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(20)30214-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181182PMC
April 2020

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

Malar J 2020 Mar 30;19(1):128. Epub 2020 Mar 30.

Division of HIV, ID, and Global Medicine, University of California, San Francisco, 1001 Potrero Ave, SFGH, Building 3, San Francisco, CA, 94110, USA.

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 < 5 years, 171,166 aged 5-15 years and 513,752 > 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 < 5 years decreased from 31 to 16% and 35 to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58 to 30% and 64 to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases > 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.
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http://dx.doi.org/10.1186/s12936-020-03196-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106889PMC
March 2020

Systematic review of the status of pfhrp2 and pfhrp3 gene deletion, approaches and methods used for its estimation and reporting in Plasmodium falciparum populations in Africa: review of published studies 2010-2019.

Malar J 2019 Nov 6;18(1):355. Epub 2019 Nov 6.

School of Medicine, College of Health Sciences Makerere University, Kampala, Uganda.

Background: Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa, where Plasmodium falciparum is predominant. However, their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp3). Use of standard and recommended methods is key for accurate investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion.

Methods: A systematic review was conducted to assess the status, methods and approaches that have been used for investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion in Africa. An online search was done using PubMed and MEDLINE Google Scholar for all articles published in English on pfhrp2/3 gene deletion in Africa. Relevant articles that met the inclusion criteria were summarized and assessed based on the protocol recommended by the World Health Organization for confirmation and reporting of pfhrp2/3 gene deletion.

Results: The search identified a total of 18 articles out of which 14 (77.7%) fulfilled the criteria for inclusion and were retained for review. The articles were distributed across 12 countries where the pfhrp2 and pfhrp3 gene deletion studies were conducted and reported. The level of pfhrp2/3 gene deletion across selected studies in Africa ranged from the highest 62% to the lowest 0.4%. There was wide variation in methods and approaches including study designs, size and sampling and whether both pfhrp2 and pfhrp3 double deletions or pfhrp2 single deletion were investigated, with a wide variation in laboratory methods.

Conclusion: Based on the review, there is evidence of the presence of pfhrp2/3 gene-deleted P. falciparum parasites in Africa. The approaches and methods used for investigation, confirmation and reporting of pfhrp2/3 deleted parasites have varied between studies and across countries. Countries that are considering plans to investigate, confirm and report pfhrp2/3 deletion should use recommended standard and harmonized methods to prevent unnecessary recommendations for costly switch of RDTs in Africa.
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http://dx.doi.org/10.1186/s12936-019-2987-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836395PMC
November 2019

Factors associated with uptake of optimal doses of intermittent preventive treatment for malaria among pregnant women in Uganda: analysis of data from the Uganda Demographic and Health Survey, 2016.

Malar J 2019 Jul 26;18(1):250. Epub 2019 Jul 26.

Uganda Public Health Fellowship Programme, Kampala, Uganda.

Background: The Uganda National Malaria Control Programme recognizes the importance of minimizing the effect of malaria among pregnant women. Accordingly, strategies including intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) have been scaled up. Uptake of IPTp-SP among pregnant women in Uganda, aged 15-49 years who had had a live birth 2 years preceding the 2016 Uganda Demographic and Health Survey (UDHS) was determined and factors associated with the uptake of optimal IPTp-SP doses were identified.

Methods: This was a secondary analysis of the UDHS 2016 dataset. The outcome variable was uptake of IPTp-SP doses among women 15-49 years old who had had a live birth 2 years preceding the survey. Independent variables were residence type, age, marital status, education, wealth status, region of residence, parity, number of antenatal care (ANC) attendance, timing to first ANC visit, and exposure to messages through radio. Logistic regression was used to identify factors associated with the uptake of optimal IPTp-SP doses.

Results: Uptake of three or more doses of IPTp-SP was 18%. The likelihood of taking optimal doses of IPTp-SP was increased among those who had attained a secondary-level education (aOR: 1.5, 95% CI 1.04-2.15), those who attended ANC ≥ 4 times (aOR: 1.34, 95% CI 1.12-1.60), and those exposed to radio messages (aOR: 1.23, 95% CI 1.02-1.48). Among those in the age category > 34 years (aOR: 0.70, 95% CI 0.53-0.92), and those who attended first ANC in the third trimester of pregnancy (aOR: 0.58, 95% CI 0.38-0.87) the odds of uptake were decreased.

Conclusions: Education status, exposure to radio messages about health and frequency of ANC attendance were associated with increased uptake while timing of first ANC attendance and being > 34 years were associated with decreased uptake. The findings suggest a need to strengthen behaviour change communication among women of child-bearing age in order to improve uptake of IPTp-SP during pregnancy.
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http://dx.doi.org/10.1186/s12936-019-2883-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660695PMC
July 2019

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.

Malar J 2019 Jun 24;18(1):207. Epub 2019 Jun 24.

London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

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.
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http://dx.doi.org/10.1186/s12936-019-2838-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591906PMC
June 2019

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.

Trials 2019 Jun 3;20(1):321. Epub 2019 Jun 3.

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.

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.
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http://dx.doi.org/10.1186/s13063-019-3382-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547536PMC
June 2019

LLIN Evaluation in Uganda Project (LLINEUP): a cross-sectional survey of species diversity and insecticide resistance in 48 districts of Uganda.

Parasit Vectors 2019 Mar 12;12(1):94. Epub 2019 Mar 12.

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.

Background: Long-lasting insecticidal nets (LLINs) are the principal tool for malaria control in Africa and are presently treated with a single class of insecticide; however, increasing levels of insecticide resistance threaten their success. In response to this threat nets have been developed that incorporate the synergist, piperonyl butoxide (PBO), which inhibits the activity of cytochrome P450s which is one main mechanisms of insecticide resistance, allowing resistance to pyrethroids to be reversed. However, data on the value and cost effectiveness of these nets is lacking. A large-scale cluster randomised trial of conventional LLINs and PBO-LLINs was conducted in Uganda in 104 health sub-districts (HSDs) in 2017-2019. Prior to the mass distribution of LLINs, a baseline entomological survey was carried out, the results of which are reported herein. Ten households from each HSD were randomly selected for entomological surveillance at baseline which included household mosquito collections.

Results: Prior to LLIN distribution entomological collections were carried out in 1029 houses across the 104 HSDs. Anopheles gambiae (s.l.) was the principal vector in all but 9 of the 71 HSDs that yielded vector species. Molecular analysis found An. gambiae (s.s.) to be the predominant vector collected. Plasmodium falciparum was detected in 5.5% of An. gambiae (s.s.) and in 4.0% of An. funestus (s.s.) examined. Infection rates of other plasmodium species (P. vivax, P. ovale and P. malariae) were lower with infection rates of 1.2% and 1.7% for An. gambiae (s.s.) and An. funestus (s.s.), respectively. The knockdown resistance (kdr) mutation Vgsc-L1014S was found at very high frequency in An. gambiae (s.s.) with the Vgsc-L1014F mutation at low frequency and the wild-type allele virtually absent. In An. arabiensis the wild-type allele was predominant. The resistance-associated alleles, Cyp4j5-L43F and Coeae1d were found at moderate frequencies which varied across the study site. Vgsc-N1575Y mutation was not found in any samples examined.

Conclusions: No significant differences between planned intervention arms was observed in vector densities, sporozoite infection rate or insecticide resistance marker frequency across the study site prior to the distribution of LLINs. Very high levels of kdr resistance were observed in all areas; however, the resistance-associated markers Cyp4j5-L43F and Coeae1d were found at varying frequencies across the study site which may have implications for the effectiveness of standard LLINs. Trial registration This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395.
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http://dx.doi.org/10.1186/s13071-019-3353-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417037PMC
March 2019

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

Sci Rep 2018 12 18;8(1):17928. Epub 2018 Dec 18.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

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.
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http://dx.doi.org/10.1038/s41598-018-36249-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298957PMC
December 2018

LLIN Evaluation in Uganda Project (LLINEUP): factors associated with ownership and use of long-lasting insecticidal nets in Uganda: a cross-sectional survey of 48 districts.

Malar J 2018 Nov 13;17(1):421. Epub 2018 Nov 13.

London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

Background: Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. To investigate factors associated with ownership and use of LLINs in Uganda, a cross-sectional community survey was conducted in March-June 2017, approximately 3 years after a national Universal Coverage Campaign (UCC).

Methods: Households from 104 clusters (health sub-districts) in 48 districts were randomly selected using two-staged cluster sampling; 50 households were enrolled per cluster. Outcomes were household ownership of LLINs (at least one LLIN), adequate LLIN coverage (at least one LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Associations between variables of interest and outcomes were made using multivariate logistic regression.

Results: In total, 5196 households, with 29,627 residents and 6980 bed-nets, were included in the analysis. Overall, 65.0% of households owned at least one LLIN (down from 94% in 2014). In the adjusted analysis, factors most strongly associated with LLIN ownership were living in a wealthier household (highest tercile vs lowest; adjusted odds ratio [aOR] 1.94, 95% CI 1.66-2.28, p < 0.001) and time since the last UCC (29-37 vs 42-53 months; aOR 1.91, 95% CI 1.60-2.28, p < 0.001). Only 17.9% of households had adequate LLIN coverage (down from 65% in 2014). Factors most strongly associated with adequate coverage were fewer residents (2-4 vs ≥ 7; aOR 6.52, 95% CI 5.13-8.29, p < 0.001), living in a wealthier household (highest tercile vs lowest; aOR: 2,32, 95% CI 1.88-2.85, p < 0.001) and time since the last UCC (29-37 vs 42-53 months; aOR 2.13, 95% CI 1.61-2.81, p < 0.001). Only 39.5% of residents used a LLIN the previous night. Age was strongly associated with LLIN use, as were household wealth and time since the last UCC. Children < 5 years (44.7%) and residents > 15 years (44.1%) were more likely to use nets than children aged 5-15 years (30.7%; < 5 years: aOR 1.71, 95% CI 1.62-1.81, p < 0.001; > 15 years: aOR 1.37, 95% CI 1.29-1.45, p < 0.001).

Conclusions: Long-lasting insecticidal net ownership and coverage have reduced markedly in Uganda since the last net distribution campaign in 2013/14. Houses with many residents, poorer households, and school-aged children should be targeted to improve LLIN coverage and use. Trial registration This study is registered with ISRCTN (17516395).
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http://dx.doi.org/10.1186/s12936-018-2571-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234693PMC
November 2018

Comparative Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Ugandan Children.

J Infect Dis 2019 03;219(7):1112-1120

Department of Medicine, University of California, San Francisco.

Background: In Uganda, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) showed excellent treatment efficacy for uncomplicated malaria in prior trials. Because the frequency of resistance to artemisinins and piperaquine is increasing in Southeast Asia and the prevalence of Plasmodium falciparum polymorphisms associated with resistance has changed, we reassessed treatment efficacies at 3 sites in Uganda.

Methods: For this randomized, single-blinded clinical trial, children aged 6-59 months with uncomplicated falciparum malaria were assigned treatment with AL or DHA-PQ and followed for 42 days. Primary end points were risks of recurrent parasitemia, either unadjusted or adjusted to distinguish recrudescence from new infection. We assessed selection by study regimens of relevant P. falciparum genetic polymorphisms associated with drug resistance.

Results: Of 599 patients enrolled, 578 completed follow-up. There were no early treatment failures. The risk of recurrent parasitemia was lower with DHA-PQ as compared to AL at all 3 sites at 42 days (26.0% vs 47.0%; P < .001). Recrudescent infections were uncommon in both the DHA-PQ and AL arms (1.1% and 2.2%, respectively; P = .25). Neither regimen selected for pfcrt or pfmdr1 polymorphisms associated with drug resistance.

Conclusions: AL and DHA-PQ remain effective for the treatment of malaria in Uganda. Neither regimen selected for genetic polymorphisms associated with drug resistance.

Clinical Trials Registration: ISRCTN15793046.
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http://dx.doi.org/10.1093/infdis/jiy637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868963PMC
March 2019

Interactions between climatic changes and intervention effects on malaria spatio-temporal dynamics in Uganda.

Parasite Epidemiol Control 2018 Aug 26;3(3):e00070. Epub 2018 Apr 26.

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland.

Background: Although malaria burden in Uganda has declined since 2009 following the scale-up of interventions, the disease is still the leading cause of hospitalization and death. Transmission remains high and is driven by suitable weather conditions. There is a real concern that intervention gains may be reversed by climatic changes in the country. In this study, we investigate the effects of climate on the spatio-temporal trends of malaria incidence in Uganda during 2013-2017.

Methods: 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. Weather data was obtained from remote sensing sources including rainfall, day land surface temperature (LSTD) and night land surface temperature (LSTN), Normalized Difference Vegetation Index (NDVI), altitude, land cover, and distance to water bodies. Spatial and temporal correlations were taken into account by assuming a conditional autoregressive and a first-order autoregressive process on district and monthly specific random effects, respectively. Fourier trigonometric functions modeled seasonal fluctuations in malaria transmission. The effects of climatic changes on the malaria incidence changes between 2013 and 2017 were estimated by modeling the difference in time varying climatic conditions at the two time points and adjusting for the effects of intervention coverage, socio-economic status and health seeking behavior.

Results: Malaria incidence declined steadily from 2013 to 2015 and then increased in 2016. The decrease was by over 38% and 20% in children <5 years and individuals ≥5 years, respectively. Temporal trends depict a strong bi-annual seasonal pattern with two peaks during April-June and October-December. The annual average of rainfall, LSTD and LSTN increased by 3.7 mm, 2.2 °C and 1.0 °C, respectively, between 2013 and 2017, whereas NDVI decreased by 6.8%. On the one hand, the increase in LSTD and decrease in NDVI were associated with a reduction in the incidence decline. On the other hand, malaria interventions and treatment seeking behavior had reverse effects, that were stronger compared to the effects of climatic changes. Important interactions between interventions with NDVI and LSTD suggest a varying impact of interventions on malaria burden in different climatic conditions.

Conclusion: Climatic changes in Uganda during the last five years contributed to a favorable environment for malaria transmission, and had a detrimental effect on malaria reduction gains achieved through interventions scale-up efforts. The NMCP should create synergies with the National Meteorological Authority with an ultimate goal of developing a Malaria Early Warning System to mitigate adverse climatic change effects on malaria risk in the country.
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http://dx.doi.org/10.1016/j.parepi.2018.e00070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020080PMC
August 2018

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

Malar J 2018 Apr 12;17(1):162. Epub 2018 Apr 12.

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, Switzerland.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1186/s12936-018-2312-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898071PMC
April 2018

Malaria incidence among children less than 5 years during and after cessation of indoor residual spraying in Northern Uganda.

Malar J 2017 08 7;16(1):319. Epub 2017 Aug 7.

Makerere University College of Health Sciences, Kampala, Uganda.

Background: In June 2015, a malaria epidemic was confirmed in ten districts of Northern Uganda; after cessation of indoor residual spraying (IRS). Epidemic was defined as an increase in incidence per month beyond one standard deviation above mean incidence of previous 5 years. Trends in malaria incidence among children-under-5-years were analysed so as to describe the extent of change in incidence prior to and after cessation of IRS.

Methods: Secondary data on out-patient malaria case numbers for children-under-5-years July 2012 to June 2015 was electronically extracted from the district health management information software2 (DHIS2) for ten districts that had IRS and ten control districts that didn't have IRS. Data was adjusted by reporting rates, cleaned by smoothing and interpolation and incidence of malaria per 1000 population derived. Population data obtained from 2002 and 2014 census reports. Data on interventions obtained from malaria programme reports, rainfall data obtained from Uganda National Meteorological Authority. Three groups of districts were created; two based on when IRS ended, the third not having IRS. Line graphs were plotted showing malaria incidence vis-à-vis implementation of IRS, mass net distribution and rainfall. Changes in incidence after withdrawal of IRS were obtained using incidence rate ratios (IRR). IRR was calculated as incidence for each month after the last IRS divided by incidence of the IRS month. Poisson regression was used to test statistical significance.

Results: Incidence of malaria declined between spray activities in districts that had IRS. Decline in IRR for 4 months after last IRS month was greater in the sprayed than control districts. On the seventh month following cessation of IRS, incidence in sprayed districts rose above that of the last spray month [1.74: 95% CI (1.40-2.15); and 1.26: 95% CI (1.05-1.51)]. Rise in IRR continued from 1.26 to 2.62 (95% CI 2.21-3.12) in June 2015 for districts that ended IRS in April 2014. Peak in rainfall occurred in May 2015.

Conclusion: There was sustained control of malaria incidence during IRS implementation. Following withdrawal and peak in rainfall, incidence rose to epidemic proportions. This suggests a plausible link between the malaria epidemic, peak in rainfall and cessation of IRS.
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http://dx.doi.org/10.1186/s12936-017-1966-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547524PMC
August 2017

Rapid reduction of malaria following introduction of vector control interventions in Tororo District, Uganda: a descriptive study.

Malar J 2017 May 30;16(1):227. Epub 2017 May 30.

School of Public Health, Makerere University, Kampala, Uganda.

Background: In 2012, Tororo District had the highest malaria burden in Uganda with community Plasmodium prevalence of 48%. To control malaria in the district, the Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and added indoor residual spraying (IRS) in 2014. This study assessed malaria incidence, test positivity rates and outpatient (OPD) attendance due to malaria before and after vector control interventions.

Methods: This study was based on analysis of Health Management Information System (HMIS) secondary malaria surveillance data of 2,727,850 patient records in OPD registers of 61 health facilities from 2012 to 2015. The analysis estimated monthly malaria incidence for the entire population and also separately for <5- and ≥5-year-olds before and after introduction of vector control interventions; determined laboratory test positivity rates and annual percentage of malaria cases in OPD. Chi square for trends was used to analyse annual change in malaria incidence and logistic regression for monthly reduction.

Results: Following universal LLINs coverage, the annual mean monthly malaria incidence fell from 95 cases in 2013 to 76 cases per 1000 in 2014 with no significant monthly reduction (OR = 0.99, 95% CI 0.96-1.01, P = 0.37). Among children <5 years, the malaria incidence reduced from 130 to 100 cases per 1000 (OR = 0.98, 95% CI 0.97-1.00, P = 0.08) when LLINs were used alone in 2014, but declined to 45 per 1000 in 2015 when IRS was combined with LLINs (OR = 0.94, 95% CI 0.91-0.996, P < 0.0001). Among individuals aged ≥5 years, mean monthly malaria incidence reduced from 59 to 52 cases per 1000 (OR = 0.99, 95% CI 0.97-1.02, P = 0.8) when LLINs were used alone in 2014, but reduced significantly to 25 per 1000 in 2015 (OR = 0.91, 95% CI 0.88-0.94, P < 0.0001). Malaria test positivity rate reduced from 57% in 2013 to 30% (Chi = 15, P < 0.0001) in 2015. Slide positivity rate reduced from 45% in 2013 to 21% in 2015 (P = 0.004) while RDT positivity declined from 69 to 40%.

Conclusions: A rapid reduction in malaria incidence was observed in Tororo District following the introduction of IRS in addition to LLINs. There was no significant reduction in malaria incidence following universal distribution of LLINs to communities before introduction of IRS.
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http://dx.doi.org/10.1186/s12936-017-1871-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450094PMC
May 2017

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

Malar J 2017 05 25;16(1):219. Epub 2017 May 25.

National Malaria Control Programme, Ministry of Health, Kampala, Uganda.

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.
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http://dx.doi.org/10.1186/s12936-017-1824-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445348PMC
May 2017

District health planning at a time of transition: a critical review and lessons learnt from the implementation of regional planning in Uganda.

Int Health 2016 05;8(3):162-9

Directorate of Planning & Development, Ministry of Health, Kampala, Uganda.

A quarter of a century after the Harare Declaration on Strengthening District Health Systems Based on Primary Health Care (1987) was conceived, district health teams (DHTs) are facing a markedly changed situation. Rapid population growth, urbanization, a rapidly developing private sector, and the increasing role of vertical programs and global initiatives have marginalized the planning process and weakened the entire district health system (DHS). The Ugandan Ministry of Health (MoH) responded to these challenges by beginning a review of district planning: a key action point of the Harare Declaration. The first step was a critical review of relevant literature, then central and district health staff were engaged with to provide their input in developing the new strategy. Through a field experiment started in 2012-13, and still underway, the MoH is developing an innovative regional approach to health planning, which aims to encompass the complexity of the new context of health care provision and coordinate all new actors (private health providers, projects and local government staff from other sectors) operating in the health sector. A strategic revision of the planning process represents an opportunity to develop an appropriate 'Theory of Change', intended as a broader approach of thinking about the entire DHS and the relative role and functions of the DHT. Leadership and stewardship capacities of MoH staff, at central and peripheral level, must be strengthened and supported to achieve the expected changes and results.
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http://dx.doi.org/10.1093/inthealth/ihw012DOI Listing
May 2016

NECT trial: more than a small victory over sleeping sickness.

Lancet 2009 Jul 24;374(9683):7-9. Epub 2009 Jun 24.

District Health Services, Moyo District Local Government, Moyo, Uganda.

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http://dx.doi.org/10.1016/S0140-6736(09)61163-6DOI Listing
July 2009
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