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1.
Malar J ; 20(1): 138, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678166

RESUMO

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. METHODS: From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). RESULTS: In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18-0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49-0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002-0.009, p < 0.001), and An. funestus sensu lato (s.l.) (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005-0.004, p < 0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07-0.33, p < 0.001). CONCLUSIONS: LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviourally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority.

2.
BMJ Open ; 11(2): e040427, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593769

RESUMO

INTRODUCTION: Drivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on Plasmodium falciparum malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses. METHODS AND ANALYSIS: We have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day 'zero'; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBER: Current Controlled Trials identifier: ISRCTN62041885.

3.
Malar J ; 20(1): 56, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478507

RESUMO

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

4.
Malar J ; 19(1): 445, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267886

RESUMO

BACKGROUND: Accurate measures of malaria incidence are essential to track progress and target high-risk populations. While health management information system (HMIS) data provide counts of malaria cases, quantifying the denominator for incidence using these data is challenging because catchment areas and care-seeking behaviours are not well defined. This study's aim was to estimate malaria incidence using HMIS data by adjusting the population denominator accounting for travel time to the health facility. METHODS: Outpatient data from two public health facilities in Uganda (Kihihi and Nagongera) over a 3-year period (2011-2014) were used to model the relationship between travel time from patient village of residence (available for each individual) to the facility and the relative probability of attendance using Poisson generalized additive models. Outputs from the model were used to generate a weighted population denominator for each health facility and estimate malaria incidence. Among children aged 6 months to 11 years, monthly HMIS-derived incidence estimates, with and without population denominators weighted by probability of attendance, were compared with gold standard measures of malaria incidence measured in prospective cohorts. RESULTS: A total of 48,898 outpatient visits were recorded across the two sites over the study period. HMIS incidence correlated with cohort incidence over time at both study sites (correlation in Kihihi = 0.64, p < 0.001; correlation in Nagongera = 0.34, p = 0.045). HMIS incidence measures with denominators unweighted by probability of attendance underestimated cohort incidence aggregated over the 3 years in Kihihi (0.5 cases per person-year (PPY) vs 1.7 cases PPY) and Nagongera (0.3 cases PPY vs 3.0 cases PPY). HMIS incidence measures with denominators weighted by probability of attendance were closer to cohort incidence, but remained underestimates (1.1 cases PPY in Kihihi and 1.4 cases PPY in Nagongera). CONCLUSIONS: Although malaria incidence measured using HMIS underestimated incidence measured in cohorts, even when adjusting for probability of attendance, HMIS surveillance data are a promising and scalable source for tracking relative changes in malaria incidence over time, particularly when the population denominator can be estimated by incorporating information on village of residence.

5.
Malar J ; 19(1): 449, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272281

RESUMO

BACKGROUND: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. METHODS: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. RESULTS: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM. CONCLUSION: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622.

6.
PLoS One ; 15(12): e0243303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270743

RESUMO

Indoor residual spraying (IRS) and long-lasting insecticide-treated bednets (LLINs) are common tools for reducing malaria transmission. We studied a cohort in Uganda with universal access to LLINs after 5 years of sustained IRS to explore LLIN adherence when malaria transmission has been greatly reduced. Eighty households and 526 individuals in Nagongera, Uganda were followed from October 2017 -October 2019. Every two weeks, mosquitoes were collected from sleeping rooms and LLIN adherence the prior night assessed. Episodes of malaria were diagnosed using passive surveillance. Risk factors for LLIN non-adherence were evaluated using multi-level mixed logistic regression. An age-matched case-control design was used to measure the association between LLIN non-adherence and malaria. Across all time periods, and particularly in the last 6 months, non-adherence was higher among both children <5 years (OR 3.31, 95% CI: 2.30-4.75; p<0.001) and school-aged children 5-17 years (OR 6.88, 95% CI: 5.01-9.45; p<0.001) compared to adults. In the first 18 months, collection of fewer mosquitoes was associated with non-adherence (OR 3.25, 95% CI: 2.92-3.63; p<0.001), and, in the last 6 months, residents of poorer households were less adherent (OR 5.1, 95% CI: 1.17-22.2; p = 0.03). Any reported non-adherence over the prior two months was associated with a 15-fold increase in the odds of having malaria (OR 15.0, 95% CI: 1.95 to 114.9; p = 0.009). Knowledge about LLIN use was high, and the most frequently reported barriers to use included heat and low perceived risk of malaria. Children, particularly school-aged, participants exposed to fewer mosquitoes, and those from poorer households, were less likely to use LLINs. Non-adherence to LLINs was associated with an increased risk of malaria. Strategies, such as behavior change communications, should be prioritized to ensure consistent LLIN use even when malaria transmission has been greatly reduced.

7.
Lancet Glob Health ; 8(12): e1499-e1511, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33222799

RESUMO

BACKGROUND: The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. METHODS: In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. FINDINGS: Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages. INTERPRETATION: Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention. FUNDING: US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship.

8.
Malar J ; 19(1): 405, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176793

RESUMO

BACKGROUND: The burden of malaria in Uganda remains high, but has become increasingly heterogenous following intensified malaria control. Travel within Uganda is recognized as a risk factor for malaria, but behaviours associated with travel are not well-understood. To address this knowledge gap, malaria-relevant behaviours of cohort participants were assessed during travel and at home in Uganda. METHODS: Residents from 80 randomly selected households in Nagongera sub-county, Tororo district were enrolled into a cohort to study malaria in rural Uganda. All participants were given long-lasting insecticidal nets (LLINs) at enrolment and were evaluated every 4 weeks at the study clinic. Participants were asked if they had travelled overnight from their home, and if so, a questionnaire was administered to capture information on travel details and behaviours. Behaviour while travelling was assessed within 4 weeks following travel during the study clinic visit. Behaviour while at home was assessed using a similar questionnaire during two-weekly home visits. Behaviours while travelling vs at home were compared using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. Analysis of factors associated with LLIN adherence, such as destination and duration of travel, time to bed during travel, gender and age at time of travel, were assessed using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. RESULTS: Between October 2017 and October 2019, 527 participants were enrolled and assessed for travel. Of these, 123 (23.2%) reported taking 211 overnight trips; 149 (70.6%) trips were within Tororo. Participants were less likely to use LLINs when travelling than when at home (41.0% vs. 56.2%, relative risk [RR] 0.73, 95% CI 0.60-0.89, p = 0.002); this difference was noted for women (38.8% vs 59.2%, RR 0.66, 95% CI 0.52-0.83, p = 0.001) but not men (48.3% vs 46.6%, RR 0.96, 95% CI 0.67-1.40, p = 0.85). In an adjusted analysis, factors associated with LLIN use when travelling included destination (travelling to districts not receiving indoor residual spraying [IRS] 65.8% vs Tororo district 32.2%, RR 1.80, 95% CI 1.31-2.46, p < 0.001) and duration of travel (> 7 nights 60.3% vs one night 24.4%, RR 1.97, 95% CI 1.07-3.64, p = 0.03). CONCLUSIONS: Travellers, particularly women, were less likely to use LLINs when travelling than when at home. LLIN adherence was higher among those who travelled to non-IRS districts and for more than 1 week, suggesting that perceived malaria risk influences LLIN use. Strategies are needed to raise awareness of the importance of using LLINs while travelling.

9.
Elife ; 92020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107430

RESUMO

Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.

10.
BMC Med ; 18(1): 207, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32772921

RESUMO

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown. METHODS: We conducted a double-blind randomized trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomized to monthly IPTp with either DP or SP. Infants were followed for all their medical care in a dedicated study clinic, and routine assessments were conducted every 4 weeks. At all visits, infants with fever and a positive thick blood smear were diagnosed and treated for malaria. The primary outcome was malaria incidence during the first 12 months of life. All analyses were done by modified intention to treat. RESULTS: Of the 782 women enrolled, 687 were followed through delivery from December 9, 2016, to December 5, 2017, resulting in 678 live births: 339 born to mothers randomized to SP and 339 born to those randomized to DP. Of these, 581 infants (85.7%) were followed up to 12 months of age. Overall, the incidence of malaria was lower among infants born to mothers randomized to DP compared to SP, but the difference was not statistically significant (1.71 vs 1.98 episodes per person-year, incidence rate ratio (IRR) 0.87, 95% confidence interval (CI) 0.73-1.03, p = 0.11). Stratifying by infant sex, IPTp with DP was associated with a lower incidence of malaria among male infants (IRR 0.75, 95% CI 0.58-0.98, p = 0.03) but not female infants (IRR 0.99, 95% CI 0.79-1.24, p = 0.93). CONCLUSION: Despite the superiority of DP for IPTp, there was no evidence of a difference in malaria incidence during infancy in infants born to mothers who received DP compared to those born to mothers who received SP. Only male infants appeared to benefit from IPTp-DP suggesting that IPTp-DP may provide additional benefits beyond birth. Further research is needed to further explore the benefits of DP versus SP for IPTp on the health outcomes of infants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02793622 . Registered on June 8, 2016.

11.
Am J Trop Med Hyg ; 103(4): 1517-1524, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32840203

RESUMO

Malaria is frequently diagnosed in urban Kampala, despite low transmission intensity. To evaluate the association between recent travel out of Kampala and malaria, we conducted a matched case-control study. Cases were febrile outpatients with a positive malaria test; controls were febrile outpatients with a negative test. For every two cases, five controls were selected, matching on age. Data were collected on recent overnight travel out of Kampala (past 60 days), destination and duration of travel, and behavioral factors, including sleeping under an insecticide-treated net (ITN) during travel. From July to August 2019, 162 cases and 405 controls were enrolled. The locations of residence of cases and controls were similar. More controls were female (62.7% versus 46.3%, P < 0.001). Overall, 158 (27.9%) participants reported recent overnight travel. Travelers were far more likely to be diagnosed with malaria than those who did not travel (80.4% versus 8.6%, OR 58.9, 95% CI: 23.1-150.1, P < 0.001). Among travelers, traveling to a district not receiving indoor residual spraying of insecticide (OR 35.0, 95% CI: 4.80-254.9, P < 0.001), no ITN use (OR 30.1, 95% CI: 6.37-142.7, P < 0.001), engaging in outdoor activities (OR 22.0, 95% CI: 3.42-141.8, P = 0.001), and age < 16 years (OR 8.36, 95% CI: 2.22-56.2, P = 0.03) were associated with increased odds of malaria. Kampala residents who traveled overnight out of the city were at substantially higher risk of malaria than those who did not travel. For these travelers, personal protection measures, including sleeping under an ITN when traveling, should be advocated.


Assuntos
Mosquiteiros Tratados com Inseticida , Malária/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Malária/parasitologia , Malária/prevenção & controle , Masculino , Viagem , Uganda/epidemiologia
12.
Am J Trop Med Hyg ; 103(4): 1525-1533, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700666

RESUMO

Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014. We describe the burden of malaria in Tororo 5 years following the initiation of IRS. We followed a cohort of 531 participants from 80 randomly selected households in Nagongera subcounty, Tororo district, from October 2017 to October 2019. Mosquitoes were collected every 2 weeks using CDC light traps in all rooms where participants slept, symptomatic malaria was identified by passive surveillance, and microscopic and submicroscopic parasitemia were measured every 4 weeks using active surveillance. Over the 2 years of follow-up, 15,780 female anopheline mosquitos were collected, the majority (98.0%) of which were Anopheles arabiensis. The daily human biting rate was 2.07, and the annual entomological inoculation rate was 0.43 infective bites/person/year. Only 38 episodes of malaria were diagnosed (incidence 0.04 episodes/person/year), and there were no cases of severe malaria or malarial deaths. The prevalence of microscopic parasitemia was 1.9%, and the combined prevalence of microscopic and submicroscopic parasitemia was 10.4%, each highest in children aged 5-15 years (3.3% and 14.0%, respectively). After 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.


Assuntos
Anopheles/parasitologia , Inseticidas/uso terapêutico , Malária/epidemiologia , Controle de Mosquitos , Mosquitos Vetores/parasitologia , Adolescente , Animais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Malária/parasitologia , Malária/prevenção & controle , Malária/transmissão , Masculino , Parasitemia/epidemiologia , Parasitemia/parasitologia , Parasitemia/transmissão , Prevalência , Uganda/epidemiologia
13.
BMC Infect Dis ; 20(1): 503, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660434

RESUMO

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.


Assuntos
Anemia/etiologia , Hospitalização , Hospitais Pediátricos , Malária/complicações , Malária/epidemiologia , Plasmodium falciparum/imunologia , Inconsciência/etiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Hospitais Públicos , Humanos , Incidência , Lactente , Malária/parasitologia , Malária/transmissão , Masculino , Morbidade , Plasmodium falciparum/isolamento & purificação , Prevalência , Estudos Retrospectivos , Uganda/epidemiologia
14.
Malar J ; 19(1): 221, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576188

RESUMO

BACKGROUND: Over the last two decades, there has been remarkable progress in malaria control in sub-Saharan Africa, due mainly to the massive deployment of long-lasting insecticidal nets and indoor residual spraying. Despite these gains, it is clear that in many situations, additional interventions are needed to further reduce malaria transmission. The World Health Organization (WHO) has promoted the Integrated Vector Management (IVM) approach through its Global Vector Control Response 2017-2030. However, prior roll-out of larval source management (LSM) as part of IVM, knowledge on ecology of larval aquatic habitats is required. METHODS: Aquatic habitats colonized by immature Anopheles and culicines vectors were characterized at three sites of low, medium and high malaria transmission in Uganda from October 2011 to June 2015. Larval surveys were conducted along transects in each site and aquatic habitats described according to type and size. Immature Anopheles, culicines and pupae from the described habitats were sampled using standard dipping methods to determine larval and pupae densities. Larvae were identified as anopheline or culicine, and counted. Pupae were not identified further. Binary logistic regression analysis was used to identify factors associated with the presence of immature Anopheles and culicines in each site. RESULTS: A total of 1205 larval aquatic habitats were surveyed and yielded a total of 17,028 anopheline larvae, 26,958 culicine larvae and 1189 pupae. Peaks in larval abundance occurred in all sites in March-May and August-October coinciding with the rainy seasons. Anopheles larvae were found in 52.4% (n = 251) of aquatic habitats in Tororo, a site of high transmission, 41.9% (n = 536) of habitats in Kanungu, a site with moderate malaria transmission, and 15.8% (n = 418) in Jinja, a site with low malaria transmission. The odds of finding larvae was highest in rice fields compared to pools in both Tororo (odds ratio, OR = 4.21, 95% CI 1.22-14.56, p = 0.02) and Kanungu (OR = 2.14, 95% CI 1.12-4.07, p = 0.02), while in Jinja the odd were highest in containers (OR = 4.55, 95% CI = 1.09-19.14, p = 0.03). In Kanungu, larvae were less likely to be found in containers compared to pools (OR = 0.26, 95% CI 0.09-0.66, p = 0.008) and river fringe (OR = 0.19, 95% CI 0.07-0.52, p = 0.001). Medium sized habitats were associated with high odds of finding larvae compared to small habitats (OR = 3.59, 95% CI 1.18-14.19, p = 0.039). CONCLUSIONS: These findings show that immature Anopheles and culicines were common in areas of high and moderate transmission but were rare in areas of low transmission. Although immature Anopheles and culicines were found in all types of water bodies, they were most common in rice fields and less common in open drains and in river fringes. Methods are needed to reduce the aquatic stages of anopheline mosquitoes in human-made habitats, particularly rice fields.

15.
Open Forum Infect Dis ; 7(5): ofaa116, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32420402

RESUMO

Background: We assessed the efficacy of artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria, with or without co-infecting Plasmodium spp., in Sumatera, Indonesia. Methods: Febrile patients aged >6 months with uncomplicated P. falciparum were randomized to receive dihydroartemisinin-piperaquine or artemether-lumefantrine, plus single-dose primaquine, and were followed for 42 days. Mixed Plasmodium infections were included; P. vivax infections received 14 days of primaquine. We retrospectively restricted the analysis to cases with polymerase chain reaction (PCR)-confirmed parasitemia. Recurrent parasitemia in follow-up was identified by species-specific nested PCR. Results: Of the 3731 participants screened, 302 were enrolled and randomized. In the dihydroartemisinin-piperaquine arm, P. falciparum infections were confirmed by PCR in 59 participants, with mixed infections in 23 (39.0%). In the artemether-lumefantrine arm, P. falciparum infections were confirmed by PCR in 55 participants, with mixed infections in 16 (29.0%). Both regimens were well tolerated, and symptoms improved rapidly in all treated participants. In the dihydroartemisinin-piperaquine arm, 1 P. falciparum recurrence (on day 7) and 6 P. malariae recurrences (1 had a mixed infection with P. falciparum) were identified during days 3-42 of follow-up. In the artemether-lumefantrine arm, 1 P. falciparum/P. malariae/P. vivax recurrence occurred on day 35. Submicroscopic persistence occurred during follow-up in 21 (37%) of 57 receiving dihydroartemisinin-piperaquine and 20 (39%) of 51 receiving artemether-lumefantrine. Conclusions: In Sumatera, both regimens effectively cleared initial parasitemia, but P. falciparum and P. malariae persisted in some individuals. Molecular species detection should be deployed in antimalarial efficacy trials in Indonesia. Trial registration: NCT02325180.

16.
Lancet ; 395(10232): 1292-1303, 2020 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-32305094

RESUMO

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.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/prevenção & controle , Sinergistas de Praguicidas/farmacologia , Butóxido de Piperonila/farmacologia , Animais , Anopheles/parasitologia , Anopheles/fisiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Resistência a Inseticidas , Malária/sangue , Masculino , Mosquitos Vetores/parasitologia , Mosquitos Vetores/fisiologia , Uganda
17.
Am J Trop Med Hyg ; 103(1): 404-414, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32274990

RESUMO

Global malaria burden is reducing with effective control interventions, and surveillance is vital to maintain progress. Health management information system (HMIS) data provide a powerful surveillance tool; however, its estimates of burden need to be better understood for effectiveness. We aimed to investigate the relationship between HMIS and cohort incidence rates and identify sources of bias in HMIS-based incidence. Malaria incidence was estimated using HMIS data from 15 health facilities in three subcounties in Uganda. This was compared with a gold standard of representative cohort studies conducted in children aged 0.5 to < 11 years, followed concurrently in these sites. Between October 2011 and September 2014, 153,079 children were captured through HMISs and 995 followed up through enhanced community cohorts in Walukuba, Kihihi, and Nagongera subcounties. Although HMISs substantially underestimated malaria incidence in all sites compared with data from the cohort studies, there was a strong linear relationship between these rates in the lower transmission settings (Walukuba and Kihihi), but not the lowest HMIS performance highest transmission site (Nagongera), with calendar year as a significant modifier. Although health facility accessibility, availability, and recording completeness were associated with HMIS incidence, they were not significantly associated with bias in estimates from any site. Health management information systems still require improvements; however, their strong predictive power of unbiased malaria burden when improved highlights the important role they could play as a cost-effective tool for monitoring trends and estimating impact of control interventions. This has important implications for malaria control in low-resource, high-burden countries.


Assuntos
Controle de Doenças Transmissíveis , Coleta de Dados/métodos , Sistemas de Informação em Saúde , Malária/epidemiologia , Assistência Ambulatorial , Criança , Pré-Escolar , Estudos de Coortes , Tomada de Decisões , Doenças Endêmicas , Monitoramento Epidemiológico , Feminino , Política de Saúde , Humanos , Incidência , Lactente , Masculino , Gestão da Saúde da População , Uganda/epidemiologia
18.
Malar J ; 19(1): 128, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228584

RESUMO

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.


Assuntos
Efeitos Psicossociais da Doença , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Inseticidas/uso terapêutico , Malária/prevenção & controle , Controle de Mosquitos/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Uganda , Adulto Jovem
19.
BMC Med ; 18(1): 47, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098634

RESUMO

BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/patogenicidade , Amodiaquina/farmacologia , Antimaláricos/farmacologia , Combinação Arteméter e Lumefantrina/farmacologia , Artemisininas/farmacologia , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Masculino
20.
BMC Med ; 18(1): 17, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31996199

RESUMO

BACKGROUND: There has been a successful push towards parasitological diagnosis of malaria in Africa, mainly with rapid diagnostic tests (mRDTs), which has reduced over-prescribing of artemisinin-based combination therapies (ACT) to malaria test-negative patients. The effect on prescribing for test-positive patients has received much less attention. Malaria infection in endemic Africa is often most dangerous for young children and those in low-transmission settings. This study examined non-prescription of antimalarials for patients with malaria infection demonstrated by positive mRDT results, and in particular these groups who are most vulnerable to poor outcomes if antimalarials are not given. METHODS: Analysis of data from 562,762 patients in 8 studies co-designed as part of the ACT Consortium, conducted 2007-2013 in children and adults, in Cameroon, Ghana, Nigeria, Tanzania, and Uganda, in a variety of public and private health care sector settings, and across a range of malaria endemic zones. RESULTS: Of 106,039 patients with positive mRDT results (median age 6 years), 7426 (7.0%) were not prescribed an ACT antimalarial. The proportion of mRDT-positive patients not prescribed ACT ranged across sites from 1.3 to 37.1%. For patients under age 5 years, 3473/44,539 (7.8%) were not prescribed an ACT, compared with 3833/60,043 (6.4%) of those aged ≥ 5 years. The proportion of < 5-year-olds not prescribed ACT ranged up to 41.8% across sites. The odds of not being prescribed an ACT were 2-32 times higher for patients in settings with lower-transmission intensity (using test positivity as a proxy) compared to areas of higher transmission. mRDT-positive children in low-transmission settings were especially likely not to be prescribed ACT, with proportions untreated up to 70%. Of the 7426 mRDT-positive patients not prescribed an ACT, 4121 (55.5%) were prescribed other, non-recommended non-ACT antimalarial medications, and the remainder (44.5%) were prescribed no antimalarial. CONCLUSIONS: In eight studies of mRDT implementation in five African countries, substantial proportions of patients testing mRDT-positive were not prescribed an ACT antimalarial, and many were not prescribed an antimalarial at all. Patients most vulnerable to serious outcomes, children < 5 years and those in low-transmission settings, were most likely to not be prescribed antimalarials, and young children in low-transmission settings were least likely to be treated for malaria. This major public health risk must be addressed in training and practice. TRIAL REGISTRATION: Reported in individual primary studies.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Padrões de Prática Médica , Adolescente , Adulto , Criança , Pré-Escolar , Assistência à Saúde/normas , Feminino , Gana , Humanos , Malária/diagnóstico , Masculino , Pessoa de Meia-Idade , Nigéria , Prescrições , Setor Privado , Tanzânia , Uganda , Adulto Jovem
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