High Malaria Transmission Season Research Articles

Persistence of Anti-SE36 Antibodies Induced by the Malaria Vaccine Candidate BK-SE36/CpG in 5-10-Year-Old Burkinabe Children Naturally Exposed to Malaria.

Information on the dynamics and decline/persistence of antibody titres is important in vaccine development. A recent vaccine trial in malaria-exposed, healthy African adults and children living in a malaria hyperendemic and seasonal area (Ouagadougou, Burkina Faso) was the first study in which BK-SE36/CpG was administered to different age groups. In 5- to 10-year-old children, the risk of malaria infection was markedly lower in the BK-SE36/CpG arm compared to the control arm. We report here data on antibody titres measured in this age-group after the high malaria transmission season of 2021 (three years after the first vaccine dose was administered). At Year 3, 83% of children had detectable anti-SE36 total IgG antibodies. Geometric mean antibody titres and the proportion of children with detectable anti-SE36 antibodies were markedly higher in the BK-SE36/CpG arm than the control (rabies) arm. The information obtained in this study will guide investigators on future vaccine/booster schedules for this promising blood-stage malaria vaccine candidate.

Seasonal Malaria Chemoprevention Therapy in Children Up To 9 Years of Age: Protocol for a Cluster-Randomized Trial Study.

Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older. The primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use. The study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali's Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study's primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be available in the event of SP resistance or drug supply shortages. A significant byproduct of this effort included bolstering district health information systems for rapid identification of severe malaria cases. The study began on July 1, 2019. Through November 2022, a total of 4556 children 3 months old to younger than 5 years were enrolled. Data collection ended in spring 2023, and the findings are expected to be published later in early 2024. Routine evaluation of antimalarial drugs is needed to establish appropriate SMC age targets. The study goals here may impact public health policy and provide alternative therapies in the event of drug shortages or resistance. ClinicalTrials.gov NCT04149106, https://clinicaltrials.gov/ct2/show/NCT04149106. DERR1-10.2196/51660.

Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: a randomized controlled trial

BackgroundAzithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission.MethodsWe evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit.ResultsWe enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18–0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32).ConclusionsWe did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections.Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020

Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017

BackgroundMalaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level.MethodsData of 1751 pregnant women from October 2013 to March 2014 and 1931 pregnant women from April 2017 to June 2017 were drawn from two cross-sectional household surveys conducted in 24 health districts of Burkina Faso. Pregnant women were tested for malaria in their household after consenting. Asymptomatic carriage was defined as a positive result from malaria rapid diagnostic tests in the absence of clinical symptoms of malaria. Anaemia was defined as haemoglobin level less than 11 g/dL in the first and third trimester and less than 10.5 g/dL in the second trimester of pregnancy.ResultsPrevalence of asymptomatic malaria in pregnancy was estimated at 23.9% (95% CI 20.2–28.0) during the high transmission season (October–November) in 2013. During the low transmission season, it was 12.7% (95% CI 10.9–14.7) between December and March in 2013–2014 and halved (6.4%; 95% CI 5.3–7.6) between April and June 2017. Anaemia prevalence was estimated at 59.4% (95% CI 54.8–63.8) during the high transmission season in 2013. During the low transmission season, it was 50.6% (95% CI 47.7–53.4) between December and March 2013–2014 and 65.0% (95% CI 62.8–67.2) between April and June, 2017.ConclusionThis study revealed that the prevalence of malaria asymptomatic carriage and anaemia among pregnant women at the community level remain high throughout the year. Thus, more efforts are needed to increase prevention measures such as IPTp–SP coverage in order to reduce anaemia and contribute to preventing low birth weight and poor pregnancy outcomes.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study

SummaryBackgroundSeasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness.MethodsFor this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted.Findings12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015–16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10–30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4–1·2) in 2016 and 0·4% (0·1–0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2–1·2]), and the quintuple mutation associated with resistance to sulfadoxine–pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1–0·5) in 2016 and 1·0% (0·6–1·6) in 2018 (prevalence ratio 4·8 [1·7–13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child.InterpretationSMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine–pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine–pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa.FundingUnitaid.

Investigating selected host and parasite factors potentially impacting upon seasonal malaria chemoprevention in Bama, Burkina Faso

BackgroundSince 2014, seasonal malaria chemoprevention (SMC) with amodiaquine–sulfadoxine–pyrimethamine (AQ–SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under 5 years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC.MethodsTwo sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 to 93 children under five, respectively, at the start of SMC and again 3 weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility.Results2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p = 0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95% CI 10.0–24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3.ConclusionThis study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.

Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger

BackgroundRapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative.MethodsA prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season.ResultsIn the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention.ConclusionsThe low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.

Effectiveness of medicine Malaria Off 200 as mass prophylaxis against Malaria in the high-risk villages of Shahdol, Madhya Pradesh

Background: Learning from the past experiences, the district health authority Shahdol has planned a mass-prophylactic activity with the Homeopathy Medicine (Malaria Off 200) in the selected high-risk villages (above 5 API) in the year 2016 Objective: The present paper reports the effectiveness of Malaria off 200 as mass-prophylactic drug in addition to routine antimalarial activities under NVBDCP in district Shahdol, Madhya pradesh in year 2016. Methodology: A Homeopathic drug Malaria Off 200 was used for the mass-prophylaxis of Malaria in high malaria transmission season in selected 28 villages of district Shahdol. The effectiveness of the drug was ascertained as “Reduction of ≥20% villages, having more than 2 malaria case in six-month period (July-December 2016)in comparison to the previous year”. Result: Of the 28 villages, seven (25%) reported Malaria case incidence equal to or less than two in six-month period (July-December 2016). In the same time period in previous year 23 (82%) villages reported Malaria case incidence more than two. So, reduction of number of villages with 'biannual Malaria case incidence’ rate was 57%. Conclusion: The short term finding validate the campaign as effective, as per the operational definition of effectiveness coined for the campaign. However, further time series studies with Autoregressive Integrated Moving Average (ARIMA) is recommended for future.

Challenges of DHS and MIS to capture the entire pattern of malaria parasite risk and intervention effects in countries with different ecological zones: the case of Cameroon

BackgroundIn 2011, the demographic and health survey (DHS) in Cameroon was combined with the multiple indicator cluster survey. Malaria parasitological data were collected, but the survey period did not overlap with the high malaria transmission season. A malaria indicator survey (MIS) was also conducted during the same year, within the malaria peak transmission season. This study compares estimates of the geographical distribution of malaria parasite risk and of the effects of interventions obtained from the DHS and MIS survey data.MethodsBayesian geostatistical models were applied on DHS and MIS data to obtain georeferenced estimates of the malaria parasite prevalence and to assess the effects of interventions. Climatic predictors were retrieved from satellite sources. Geostatistical variable selection was used to identify the most important climatic predictors and indicators of malaria interventions.ResultsThe overall observed malaria parasite risk among children was 33 and 30% in the DHS and MIS data, respectively. Both datasets identified the Normalized Difference Vegetation Index and the altitude as important predictors of the geographical distribution of the disease. However, MIS selected additional climatic factors as important disease predictors. The magnitude of the estimated malaria parasite risk at national level was similar in both surveys. Nevertheless, DHS estimates lower risk in the North and Coastal areas. MIS did not find any important intervention effects, although DHS revealed that the proportion of population with an insecticide-treated nets access in their household was statistically important. An important negative relationship between malaria parasitaemia and socioeconomic factors, such as the level of mother’s education, place of residence and the household welfare were captured by both surveys.ConclusionTiming of the malaria survey influences estimates of the geographical distribution of disease risk, especially in settings with seasonal transmission. In countries with different ecological zones and thus different seasonal patterns, a single survey may not be able to identify all high risk areas. A continuous MIS or a combination of MIS, health information system data and data from sentinel sites may be able to capture the disease risk distribution in space across different seasons.

Comparability of Inflammation-Adjusted Vitamin A Deficiency Estimates and Variance in Retinol Explained by C-Reactive Protein and α1-Acid Glycoprotein during Low and High Malaria Transmission Seasons in Rural Zambian Children.

Inflammation-induced hyporetinolemia (IIH), a reduction in serum retinol (SR) during inflammation, may bias population estimates of vitamin A deficiency (VAD). The optimal adjustment for IIH depends on the type and extent of inflammation. In rural Zambian children (4-8 years, N = 886), we compared three models for defining inflammation: α-1-acid glycoprotein (AGP) only (inflammation present if > 1 g/L or normal if otherwise), C-reactive protein (CRP) only (moderate inflammation, 5-15 mg/L; high inflammation, > 15 mg/L; or normal if otherwise) and a combined model using both AGP and CRP to delineate stages of infectious episode. Models were compared with respect to 1) the variance in SR explained and 2) comparability of inflammation-adjusted VAD estimated in low and high malaria seasons. Linear regression was used to estimate the variance in SR explained by each model and in estimating the adjustment factors used in generating adjusted VAD (retinol < 0.7 μmol/L). The variance in SR explained were 2% (AGP-only), 11% (CRP-only), and 11% (AGP-CRP) in the low malaria season; and 2% (AGP-only), 15% (CRP-only), and 12% (AGP-CRP) in the high malaria season. Adjusted VAD estimates in the low and high malaria seasons differed significantly for the AGP (8.2 versus 13.1%) and combined (5.5 versus 9.1%) models but not the CRP-only model (6.1 versus 6.3%). In the multivariate regression, a decline in SR was observed with rising CRP (but not AGP), in both malaria seasons (slope = -0.06; P < 0.001). In this malaria endemic setting, CRP alone, as opposed to CRP and AGP, emerged as the most appropriate model for quantifying IIH.

Malaria exacerbates inflammation-associated elevation in ferritin and soluble transferrin receptor with only modest effects on iron deficiency and iron deficiency anaemia among rural Zambian children.

In 4- to 8-year-old Zambian children (n = 744), we evaluated the effects of adjusting for inflammation (α1-acid glycoprotein >1 g/l), with or without additional adjustment for malaria, on prevalence estimates of iron deficiency (ID) and iron deficiency anaemia (IDA) during low malaria (LowM) and high malaria (HighM) transmission seasons. To estimate adjustment factors, children were classified as: (i) reference (malaria negative without inflammation), (ii) inflammation without malaria (I), (iii) malaria without inflammation (M) and (iv) inflammation with malaria (IM). We estimated the unadjusted ID or IDA prevalence, and then adjusted for inflammation alone (IDI or IDAI ) or inflammation and malaria (IDIM or IDAIM ). Mean ferritin was 38 (reference), 45 (I), 43 (M) and 54 μg/l (IM) in LowM, increasing to 44, 56, 96 and 167 μg/l, respectively, in HighM. Corresponding mean sTfR was 6.4, 6.9, 7.9 and 8.4 mg/l in LowM, increasing to 8.2, 9.2. 8.7 and 9.7 mg/l in HighM. Ferritin-based ID, IDI and IDIM were 7.8%, 8.7% or 9.1%, respectively, in LowM and 4.6%, 10.0% or 11.7%, respectively, in HighM. Corresponding soluble transferrin receptor (sTfR)-based estimates were 27.0%, 24.1% and 19.1%, respectively, in LowM, increasing to 53.6%, 46.5% and 45.3%, respectively, in HighM. Additional adjustment for malaria resulted in a ~1- to 2-percentage point change in IDA, depending on biomarker and season. In this population, malaria substantially increased ferritin and sTfR concentrations, with modest effects on ID and IDA prevalence estimates.

A village level cluster-randomized entomological evaluation of combination long-lasting insecticidal nets containing pyrethroid plus PBO synergist in Southern Mali

BackgroundThere is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs). Combination LLINs are designed to control susceptible and pyrethroid-resistant mosquito populations through a mixture of pyrethroid with piperonyl butoxide (PBO) synergist. A cluster randomized trial with entomology outcome measures was conducted in Mali to determine the added benefit over mono-treated pyrethroid predecessors. Four LLIN treatments; permethrin + PBO, permethrin, deltamethrin + PBO, and deltamethrin, were randomly allocated to four villages each (16 villages total) and distributed to cover every sleeping place. Entomological monitoring of indoor Anopheles resting densities, host preference, vector longevity, and sporozoite rates were monitored every 2 months over 2 years in 2014 and 2015.ResultsBottle bioassays confirmed permethrin and deltamethrin resistance in Anopheles gambiae sensu lato (s.l.), (the predominant species throughout the study) with pre-exposure to PBO indicating partial involvement of oxidases. Between 2014 and 2015 the mean indoor resting density was greater in the deltamethrin + PBO LLIN arm than the deltamethrin LLIN arm at 3.05 (95% CI 3.00–3.10) An. gambiae s.l. per room per day compared with 1.9 (95% CI 1.87–1.97). There was no significant difference in sporozoite rate at 3.97% (95% CI 2.91–5.02) for the deltamethrin LLIN arm and 3.04% (95% CI 2.21–3.87) for deltamethrin + PBO LLIN arm (P = 0.17). However, when analysed by season there was some evidence that the sporozoite rate was lower in the deltamethrin + PBO LLIN arm than deltamethrin LLIN arm during the rainy/high malaria transmission seasons at 1.95% (95% CI 1.18–2.72) and 3.70% (95% CI 2.56–4.84) respectively (P = 0.01).ConclusionsWhile there was some evidence that An. gambiae s.l. sporozoite rates were lower in villages with deltamethrin + PBO LLINs during the high malaria transmission seasons of 2014–2015, there was no reduction in parity rates or indoor resting densities. There was also no evidence that permethrin + PBO LLINs provided any improved control when compared with permethrin LLINs. Combination nets may have a greater impact in areas where mixed function oxidases play a more important role in pyrethroid resistance.

Antibody responses to P. falciparum blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso

BackgroundHigh parasite-specific antibody levels are generally associated with low susceptibility to Plasmodium falciparum malaria. This has been supported by several studies in which clinical malaria cases of P. falciparum malaria were reported to be associated with low antibody avidities. This study was conducted to evaluate the role of age, malaria transmission intensity and incidence of clinical malaria in the induction of protective humoral immune response against P. falciparum malaria in children living in Burkina Faso.MethodsWe combined levels of IgG and IgG subclasses responses to P. falciparum antigens: Merozoite Surface Protein 3 (MSP3), Merozoite Surface Protein 2a (MSP2a), Merozoite Surface Protein 2b (MSP2b), Glutamate Rich Protein R0 (GLURP R0) and Glutamate Rich Protein R2 (GLURP R2) in plasma samples from 325 children under five (05) years with age, malaria transmission season and malaria incidence.ResultsWe notice higher prevalence of P. falciparum infection in low transmission season compared to high malaria transmission season. While, parasite density was lower in low transmission than high transmission season. IgG against all antigens investigated increased with age. High levels of IgG and IgG subclasses to all tested antigens except for GLURP R2 were associated with the intensity of malaria transmission. IgG to MSP3, MSP2b, GLURP R2 and GLURP R0 were associated with low incidence of malaria. All IgG subclasses were associated with low incidence of P. falciparum malaria, but these associations were stronger for cytophilic IgGs.ConclusionsOn the basis of the data presented in this study, we conclude that the induction of humoral immune response to tested malaria antigens is related to age, transmission season level and incidence of clinical malaria.

Dynamic study of Anopheles gambiae s.l. population and polymorphism of TRP1 gene during high malaria transmission season in Bancoumana commune, Mali

Malaria vector control strategy is a key component of malaria control, it can interrupt malaria transmission. The effective use of this strategy is based on a depth knowledge of vector life cycle and the environmental factors that influence its life. The aims of this study was to determine the dynamics of the adult population of An.gambiae s.l. and to evaluate the allelic polymorphism of TEP1 gene implicate in malaria parasite lysis. This was conducted in endemic malaria areas Nanguilabougou and its hamlet of culture Kouroubabougou in the rural commune of Bancoumana between June 2014 and November 2015 during the high malaria transmission season. Mosquitoes were collected using light traps, stored in 50-ml tubes containing ethanol 70%, processed in the laboratory using PCR (DNA extraction, species identification and genotyping). In 2014 a total of 1433 mosquitoes were collected, An coluzzii was predominant 72.2% (n= 1034) follow by An gambiae 21.1% and hybrid An coluzzii/gambiae 3.1%. The same situation was observed in 2015 with 6612 mosquitoes collected, An coluzzii 72.4% follow by An gambiae 16.7% and hybrid An. coluzzii/gambiae 0.4%. Two An. arabiensis were found only in 2015. A strong presence of the genotype R1/R1 within An. coluzzii 85.2% in 2014 and 66.2% in 2015 was observed. An. gambiae was more associated with the S1/S1 genotype in 2014 and with the S1/R2 allele in 2015. The other allele were founded at low frequency. An. coluzzii is the most predominant during high malaria transmission season among An. gambiae s.l. species. It is also carried the high frequency TEP1 gene implicate in malaria parasite lysis.

An epidemiological study to assess Plasmodium falciparum parasite prevalence and malaria control measures in Burkina Faso and Senegal

BackgroundMalariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries.MethodsThis cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Saponé) and two sites with low malaria endemicity in Senegal (Keur Socé and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months–4 years and 5–9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors.ResultsPlasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Saponé in the 6 months–4 years age group, and 75.4% in Nouna and 70.1% in Saponé in the 5–9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6–97.0 and 64.7–80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence.ConclusionsPlasmodium falciparum infection prevalence in children younger than 10 years was 57.5% in Burkina Faso and 0.9% in Senegal, and variability was observed, among others, by age, study site and malaria control measures.

A MALARIA VACCINE SITE CHARACTERISATION: PREVALENCE AND SPECIES DISTRIBUTION OF PLASMODIUM MALARIA IN A MALARIA ENDEMIC SETTING OF BURKINA FASO (WEST AFRICA)

BackgroundAny development of a vaccine strategy or its implementation is based on a good knowledge of the biology of the pathogen and its temporal and spatial distribution. In the case...

Provider compliance to artemisinin-based combination therapy at primary health care facilities in the middle belt of Ghana.

BackgroundIn 2004, Ghana implemented the artemisinin-based combination therapy (ACT) policy. Health worker (HW) adherence to the national malaria guidelines on case-management with ACT for children below 5 years of age and older patients presenting at health facilities (HF) for primary illness consultations was evaluated 5 years post-ACT policy change.MethodsCross-sectional surveys were conducted from 2010 to 2011 at HFs that provide curative care as part of outpatient activities in two districts located in the middle belt of Ghana to coincide with the periods of low and high malaria transmission seasons. A review of patient medical records, HW interviews, HF inventories and finger-pricked blood obtained for independent malaria microscopy were used to assess HW practices on malaria case-management.ResultsData from 130 HW interviews, 769 patient medical records at 20 HFs over 75 survey days were individually linked and evaluated. The majority of consultations were performed at health centres/clinics (68.3 %) by medical assistants (28.6 %) and nurse aids (23.5 %). About 68.4 % of HWs had received ACT-specific training and 51.9 %, supervisory visits in the preceding 6 months. Despite the availability of malaria diagnostic test at most HFs (94 %), only 39.8 % (241) out of 605 (78.7 %) patients who reported fever were investigated for malaria. Treatment with ACT in line with the guidelines was 66.7 %; higher in <5 children compared to patients ≥5 years old. Judged against reference microscopy, only 44.8 % (107/239) of ACT prescriptions that conformed to the guidelines were “truly malaria”. Multivariate logistic regression analysis showed that HW were significantly more likely to comply with the guidelines if treatment were by low cadre of health staff, were for children below 5 years of age, and malaria test was performed.ConclusionAlthough the majority of patients presenting with malaria received treatment according to the national malaria guidelines, there were widespread inappropriate treatment with ACT. Compliance with the guidelines on ACT use was low, 5 years post-ACT policy change. The Ghana NMCP needs to strengthen HW capacity on malaria case-management through regular training supported by effective laboratory quality control measures.

Effect of a Malaria Control Program on the Prevalence of Malaria, Fever and Anaemia in Children under Five Years in the Hohoe Municipality of Ghana: A Comparative Analysis of Cross-Sectional Surveys

Background: Malaria and anaemia continue to adversely impact the health of children in Ghana. Hohoe is an area of intense and prolonged, seasonal malaria transmission. In 2006, malaria control programme activities which provided In-secticide Treated Bed-Nets (ITNs) to resident children under five years and Artemisinin Combination Therapies (ACTs) for the management of malaria were introduced into the Hohoe Municipality. Before the introduction of the control programme, baseline surveys were carried out in communities in the Hohoe municipality to determine the prevalence of malaria, fever, anaemia, malaria parasite density, gametocytaemia and ITN ownership and use in June and November 2006 ahead of the intervention programme. Similar surveys were conducted in 2010 after the intervention to assess changes in the earlier indicators in the same communities. This report presents an evaluation of the intervention by comparing findings before and after the malaria control interventions. Methods: In 2010, two community-based surveys were carried out in thirty communities among children aged five years and below. The first one was at the beginning of the rainy and high malaria transmission season in June and the other was in November at the end of the rainy season. The surveys were to determine the prevalence of malaria, fever, anaemia and ITN ownership, use and effectiveness among children less than 5 years. Data were collected in the form of interviews using questionnaire and collection of biological samples. Findings were compared to those similar surveys conducted in the same communities and age groups in 2006. Pr-testi was used to analyze two sample tests for proportions and t-test was used for means. Findings: Malaria prevalence decreased by 20% [9.0% vs. 7.2%; p = 0.0.40], fever decreased by 47.8% [2.3% vs. 1.2%; p = 0.008] and anaemia decreased by 32.9% [7.8% vs. 5.3%; p = 0.002]. ITN ownership increased by 67.9% [20.8% vs. 64.8%; p < 0.001], ITN use increased by 64.2% [15.1% vs. 42.2%; p < 0.001] and ITN effectiveness increased by 41.7% [20.0% vs. 34.3%; p < 0.001]. The proportion of children with high density parasitaemia reduced by 17.9% [2.8% vs. 2.3%; p = 0.223]. Gameto-cytaemia decreased by 82.5% [0.8% vs. 0.14%; p = 0.002. Similarly data comparing 2006 and 2010 post-rainy season showed that malaria prevalence decreased by 16.8% [40.4% vs. 33.6%; p < 0.001], fever decreased by 14% [5.0% vs. 4.3%; p = 0.347] and anaemia decreased by 64.2% [12% vs. 4.3%; p < 0.001]. The proportion of children with high density parasitaemia also reduced by 69.5% [10.5% vs. 3.2%; p < 0.001] and gametocytaemia decreased by 78.5% [0.8% vs. 0.17%; p = 0.008]. Conclusion: This study suggested that there was an association between the current intervention and reduction in the prevalence of malaria, fever and anaemia. High parasite density and gametocytaemia prevalence have also significantly reduced over the five years of the introduction of the control measures. There has also been a significant increase in the ownership and use of ITNs.

Clinical malaria case definition and malaria attributable fraction in the highlands of western Kenya.

BackgroundIn African highland areas where endemicity of malaria varies greatly according to altitude and topography, parasitaemia accompanied by fever may not be sufficient to define an episode of clinical malaria in endemic areas. To evaluate the effectiveness of malaria interventions, age-specific case definitions of clinical malaria needs to be determined. Cases of clinical malaria through active case surveillance were quantified in a highland area in Kenya and defined clinical malaria for different age groups.MethodsA cohort of over 1,800 participants from all age groups was selected randomly from over 350 houses in 10 villages stratified by topography and followed for two-and-a-half years. Participants were visited every two weeks and screened for clinical malaria, defined as an individual with malaria-related symptoms (fever [axillary temperature ≥ 37.5°C], chills, severe malaise, headache or vomiting) at the time of examination or 1–2 days prior to the examination in the presence of a Plasmodium falciparum positive blood smear. Individuals in the same cohort were screened for asymptomatic malaria infection during the low and high malaria transmission seasons. Parasite densities and temperature were used to define clinical malaria by age in the population. The proportion of fevers attributable to malaria was calculated using logistic regression models.ResultsIncidence of clinical malaria was highest in valley bottom population (5.0% cases per 1,000 population per year) compared to mid-hill (2.2% cases per 1,000 population per year) and up-hill (1.1% cases per 1,000 population per year) populations. The optimum cut-off parasite densities through the determination of the sensitivity and specificity showed that in children less than five years of age, 500 parasites per μl of blood could be used to define the malaria attributable fever cases for this age group. In children between the ages of 5–14, a parasite density of 1,000 parasites per μl of blood could be used to define the malaria attributable fever cases. For individuals older than 14 years, the cut-off parasite density was 3,000 parasites per μl of blood.ConclusionClinical malaria case definitions are affected by age and endemicity, which needs to be taken into consideration during evaluation of interventions.

Intermittent Use Of Sufadoxine-Pyrimethamine To Prevent Malaria In Patients With SCD In Malaria Endemic Regions: Findings From The Sickle Cell Disease Research and Control Center Of Bamako, Mali

Sickle cell disease (SCD) is a chronic disorder affecting erythrocytes and is especially prevalent throughout Sub-Saharan Africa where malaria is thought to be a significant cause of morbidity and mortality in affected individuals. In the absence of effective malaria vaccine, one of the affordable alternatives to prevent malaria at present is chemoprophylaxis. In order to evaluate the effectiveness of a monthly intermittent prophylaxis treatment (IPT) with sulfadoxine-pyrimethamine (SP) during high malaria transmission season in patients with sickle cell disease, two groups of SCD patients from two different sites were compared. The first group constituted of patients followed at the Sickle Cell Disease Research and Control Center of Bamako where IPT is routinely administered while the second group consisted of individuals enrolled in the health district in the same locality but no malaria prophylaxis. In this area, the incidence of resistance of P.falciparum to SP is estimated < 10%. SP combination was administrated as follows: sulfadoxine 25mg/kg and pyrimethamine 1.25mg/kg. For both groups, diagnosis of malaria was performed by using the rapid diagnosis test for the presence of P.falciparum. From 2011 to 2012, 687 SCD patients (457 from the Sickle Cell Disease Research and Control Center and 115 from the health district) were enrolled. The observed prevalence of malaria infection in the group receiving a monthly IPT by SP (1.5%) was much lower than the group (6%) for which IPT was not offered (P=0.01). When data was stratified by hemoglobin genotypes, malaria was found to occur entirely in SS and SC patients and no malaria cases were observed in S/β-thalassemia patients. SP was well tolerated since no patient in SP arm reported pruritus and no serious adverse events including death were recorded during the study. In malaria endemic areas where the incidence of resistance to SP is low, anti-malarial prophylaxis with this combination therapy significantly reduced the incidence of malaria in SCD patients with good safety and a lower cost. Disclosures:No relevant conflicts of interest to declare.