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BackgroundParasite prevalence is a key metric used to quantify the burden of malaria and assess the impact of control strategies. Most published estimates of parasite prevalence are based on microscopy and likely underestimate true prevalence.MethodsThick smear microscopy was performed in cohorts of children (aged 6 month to 10 years) and adults every 90 days over 2 years, at three sites of varying transmission intensity in Uganda. Microscopy-negative samples were tested for sub-microscopic parasitaemia using loop-mediated isothermal amplification (LAMP). Generalized estimating equation models were used to evaluate associations between age and parasitaemia, factors associated with sub-microscopic infection and associations between parasitaemia and haemoglobin.ResultsA total of 9260 samples were collected from 1245 participants. Parasite prevalence among children across the three sites was 7.4, 9.4 and 28.8 % by microscopy and 21.3, 31.8 and 69.0 % by microscopy plus LAMP. Parasite prevalence among adults across the three sites was 3.1, 3.0 and 5.2 % by microscopy and 18.8, 24.2 and 53.5 % by microscopy plus LAMP. Among those with parasitaemia, adults and persons recently treated with anti-malarial therapy had the highest prevalence of sub-microscopic infection. Children with sub-microscopic or microscopic parasitaemia had lower mean haemoglobin levels compared to children with no detectable parasites.ConclusionsAcross a range of transmission intensities in Uganda, microscopy vastly underestimated parasite prevalence, especially among adults.

BackgroundSubmicroscopic malaria parasitaemia is common in both high- and low-endemicity settings, but its clinical consequences are unclear.MethodsA cohort of 364 children (0.5–10 years of age) and 106 adults was followed from 2011 to 2016 in Tororo District, Uganda using passive surveillance for malaria episodes and active surveillance for parasitaemia. Participants presented every 90 days for routine visits (n = 9075); a subset was followed every 30 days. Participants who presented with fever and a positive blood smear were treated for malaria. At all routine visits microscopy was performed and samples from subjects with a negative blood smear underwent loop-mediated isothermal amplification for detection of plasmodial DNA.ResultsSubmicroscopic parasitaemia was common; the proportion of visits with submicroscopic parasitemia was 25.8% in children and 39.2% in adults. For children 0.5–10 years of age, but not adults, having microscopic and submicroscopic parasitaemia at routine visits was significantly associated with both fever (adjusted risk ratios [95% CI], 2.64 [2.16–3.22], 1.67 [1.37–2.03]) and non-febrile illness (aRR [CI], 1.52 [1.30–1.78], 1.26 [1.09–1.47]), compared to not having parasitaemia. After stratifying by age, significant associations were seen between submicroscopic parasitaemia and fever in children aged 2–< 5 and 5–10 years (aRR [CI], 1.42 [1.03–1.98], 2.01 [1.49–2.71]), and submicroscopic parasitaemia and non-febrile illness in children aged 5–10 years (aRR [CI], 1.44 [1.17–1.78]). These associations were maintained after excluding individuals with a malaria episode within the preceding 14 or following 7 days, and after adjusting for household wealth.ConclusionsSubmicroscopic malaria infections were associated with fever and non-febrile illness in Ugandan children. These findings support malaria control strategies that target low-density infections.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2221-9) contains supplementary material, which is available to authorized users.

Persistent parasitemia despite dramatic reduction in malaria incidence after 3 rounds of indoor residual spraying in Tororo, Uganda.

BackgroundArtemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV.MethodsA longitudinal, randomized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4-22 months in Tororo, Uganda. Participants were randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes. Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment. This study was registered in ClinicalTrials.gov (registration # NCT00527800).ResultsA total of 122 children were randomized to AL and 124 to DP, resulting in 412 and 425 treatments, respectively. Most adverse events were rare, with only cough, diarrhoea, vomiting, and anaemia occurring in more than 1% of treatments. There were no differences in the risk of these events between treatment groups. Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms. Retreatment for malaria within 17-28 days was associated with an increased risk of vomiting in the DP treatment arm (HR = 6.47, 95% CI 2.31-18.1, p < 0.001). There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis.ConclusionBoth AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children.Trial RegistrationClinicalTrials.gov: NCT00527800; http://clinicaltrials.gov/ct2/show/NCT00527800