Malaria and COVID-19 prevalence in a population of febrile children and adolescents living in Libreville.

Background: Patients with acute febrile illness need to be screened for malaria and coronavirus disease 2019 (COVID-19) in malaria-endemic areas to reduce malaria mortality rates and to prevent the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: To estimate the frequency of children and adolescents with COVID-19 and/or malaria among febrile patients attending for malaria diagnosis. Method: This cross-sectional study was conducted in a sentinel site for malaria surveillance during the SARS-CoV-2 pandemic (Omicron variant), from October 2021 to December 2021 in Gabon. All febrile patients were tested for malaria using microscopy. Severe acute respiratory syndrome coronavirus 2 was detected by real time polymerase chain reaction (RT-PCR) and rapid antigen tests developed by Sansure Biotech®. Results: A total of 135 patients were screened. Their median age was 6 (interquartile range [IQR]: 3-14) years. Malaria was confirmed for 49 (36.3%) patients, 29 (32.5%) children, 13 (59.0%) adolescents and 7 (29.2%) adults. The frequency of COVID-19 cases was 7.4% (n = 10/135), and it was comparable between children (n = 6; 6.7%), adolescents (n = 2; 9.1%) and adults (n = 2; 8.3%) (p = 0.17). Malaria and COVID-19 co-infections were diagnosed in 3 (6.1%) patients from all the age groups. Participants with a co-infection had a higher median temperature, a higher median parasitaemia, and were mostly infected with non-falciparum malaria. Conclusion: COVID-19 cases and cases of malaria/COVID-19 co-infections were found in febrile children and adolescents. SARS-CoV-2 testing should be included in the screening of suspected malaria cases. Contribution: This study highlights the presence of malaria-COVID-19 coinfection among children and adolescents who should also be screened for both diseases, like for adults.

Early Alterations of QTc in Patients with COVID-19 Treated with Hydroxychloroquine or Chloroquine in Libreville, Gabon.

The objective of this study was to analyze the effect of hydroxychloroquine or chloroquine associated with azithromycin on the QTc interval in Gabonese patients treated for COVID-19. METHODS: This was an observational study conducted from April to June 2020, at the Libreville University Hospital Center in Gabon. Patients admitted for COVID-19 and treated with hydroxychloroquine or chloroquine, each combined with azithromycin were included. The QTc interval was measured upon admission and 48 h after starting treatment. The primary endpoint was QTc prolongation exceeding 60 ms and/or a QTc value exceeding 500 ms at 48 h. RESULTS: Data from 224 patients, 102 (45.5%) who received hydroxychloroquine and 122 treated with chloroquine, were analyzed. The median baseline QTc was 396 (369-419) ms. After 48 h of treatment, 50 (22.3%) patients had a significant prolongation of QTc. This tended to be more frequent in patients treated with chloroquine (n = 33; 27.0%) than in those treated with hydroxychloroquine (n = 17; 16.7%) (p = 0.06). QTc prolongation exceeding 60 ms was found in 48 (21.3%) patients, while 11 patients had a (4.9%) QTc exceeding 60 ms at admission and exceeding 500 ms after 48 h. CONCLUSION: Early QTc prolongation is frequent in COVID-19 patients treated with hydroxychloroquine or chloroquine in association with azithromycin.

Performance of Field's Stain Compared with Conventional Giemsa Stain for the Rapid Detection of Blood Microfilariae in Gabon.

Filarial infections caused by Loa loa and Mansonella perstans are a considerable public health burden in rural regions of Central Africa. Rapid diagnostic tools for the detection of microfilariae in the blood are needed. Field's stain is a rapid staining technique for microscopic slides originally established for malaria diagnostics. It requires less than 1 minute of staining compared with conventional staining protocols requiring at least 15 to 20 minutes for staining and could thus significantly accelerate diagnostics for human filariasis. Here we evaluated Field's stain as a rapid staining technique in comparison to Giemsa stain for the detection of microfilariae in peripheral blood. Blood smears were collected from 175 participants residing in the region of Lambaréné and Fougamou, Gabon. Each participant's samples were stained in parallel with Field's stain and conventional Giemsa stain. Slides were then microscopically assessed and compared for qualitative and quantitative results by a blinded assessor for the two endemic filarial blood pathogens M. perstans and L. loa. Field's stain shows excellent diagnostic performance characteristics for L. loa microfilariae compared with Giemsa staining. Concordance was favorable for M. perstans although lower than for L. loa. Field's stain offers a rapid alternative to Giemsa stain for detection of L. loa microfilariae in thick blood smears. This could help accelerate diagnostics of blood filarial pathogens in mass screening programs or resource constrained health care institutions with high patient load.

Could pooled samples method affect SARS-CoV-2 diagnosis accuracy using BGI and Sansure-Biotech RT-PCR kits used in Gabon, Central Africa?

This study aims at establishing specimens pooling approach for the detection of SARS-CoV-2 using the RT-PCR BGI and Sansure-Biotech kits used in Gabon. To validate this approach, 14 positive samples, stored at -20°C for three to five weeks were analyzed individually (as gold standard) and in pools of five, eight and ten in the same plate. We created 14 pools of 5, 8 and 10 samples using 40 µL from each of the selected positive samples mixed with 4, 7 and 9 confirmed negative counterparts in a total volume of 200 µL, 320 µL and 400 µL for the pools of 5, 8 and 10 respectively. Both individual and pooled samples testing was conducted according to the BGI and Sansure-Biotech RT-PCR protocols used at the Professor Daniel Gahouma Laboratory (PDGL). Furthermore, the pooling method was also tested by comparing results of 470 unselected samples tested in 94 pools and individually. Results of our experiment showed that using a BGI single positive sample with cycle threshold (Ct) value of 28.42, confirmed by individual testing, detection occurred in all the pools. On the contrary samples with Ct >31 were not detected in pools of 10 and for these samples (Ct value as high as 37.17) their detection was possible in pool of 8. Regarding the Sansure-Biotech kit, positive samples were detected in all the pool sizes tested, irrespective of their Ct values. The specificity of the pooling method was 100% for the BGI and Sansure-Biotech RT-PCR assays. The present study found an increase in the Ct values with pool size for the BGI and Sansure-Biotech assays. This trend was statistically significant (Pearson's r = 0.978; p = 0,022) using the BGI method where the mean Ct values were 24.04±1.1, 26.74±1.3, 27.91±1.1 and 28.32±1.1 for the individual, pool of 5, 8 and 10 respectively. The testing of the 470 samples showed that one of the 94 pools had a positive test similar to the individual test using the BGI and Sansure-Biotech kits. The saving of time and economizing test reagents by using the pooling method were demonstrated in this study. Ultimately, the pooling method could be used for the diagnosis of SARS-CoV-2 without modifying the accuracy of results in Gabon. We recommend a maximum pool size of 8 for the BGI kit. For the Sansure-Biotech kit, a maximum pool size of 10 can be used without affecting its accuracy compared to the individual testing.

Malaria and COVID-19 prevalence in a population of febrile children and adolescents living in Libreville

Background: Patients with acute febrile illness need to be screened for malaria and coronavirus disease 2019 (COVID-19) in malaria-endemic areas to reduce malaria mortality rates and to prevent the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: To estimate the frequency of children and adolescents with COVID-19 and/or malaria among febrile patients attending for malaria diagnosis Method: This cross-sectional study was conducted in a sentinel site for malaria surveillance during the SARS-CoV-2 pandemic (Omicron variant), from October 2021 to December 2021 in Gabon. All febrile patients were tested for malaria using microscopy. Severe acute respiratory syndrome coronavirus 2 was detected by real time polymerase chain reaction (RT-PCR) and rapid antigen tests developed by Sansure Biotech®. Results: A total of 135 patients were screened. Their median age was 6 (interquartile range [IQR]: 3­14) years. Malaria was confirmed for 49 (36.3%) patients, 29 (32.5%) children, 13 (59.0%) adolescents and 7 (29.2%) adults. The frequency of COVID-19 cases was 7.4% (n = 10/135), and it was comparable between children (n = 6; 6.7%), adolescents (n = 2; 9.1%) and adults (n = 2; 8.3%) (p = 0.17). Malaria and COVID-19 co-infections were diagnosed in 3 (6.1%) patients from all the age groups. Participants with a co-infection had a higher median temperature, a higher median parasitaemia, and were mostly infected with non-falciparum malaria. Conclusion: COVID-19 cases and cases of malaria/COVID-19 co-infections were found in febrile children and adolescents. SARS-CoV-2 testing should be included in the screening of suspected malaria cases.

Correction to: Persistence of High In Vivo Efficacy and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine as the First- and Second-Line Treatments for Uncomplicated Plasmodium falciparum Malaria 10 Years After Their Implementation in Gabon.

Unfortunately two errors appeared in this article.

Persistence of High In Vivo Efficacy and Safety of Artesunate-Amodiaquine and Artemether-Lumefantrine as the First- and Second-Line Treatments for Uncomplicated Plasmodium falciparum Malaria 10 Years After Their Implementation in Gabon.

PURPOSE: Artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) have been widely used for the treatment of uncomplicated Plasmodium falciparum malaria since 2005 in Gabon. Since 2011, a rebound of malaria morbidity has been observed in this country, while no survey evaluating ACT efficacy was performed. During the same period, parasite resistance against artemisinin has been reported in Asia. The aim of this study was to assess the efficacy and tolerability of these two drugs in two sentinel sites of Gabon 10 years after their implementation. METHODS: Children aged from 12 to 144 months with uncomplicated malaria were recruited at the Regional Hospital of Melen, Libreville and in the Urban Health Center of Franceville between March 2014 and September 2015. The therapeutic efficacy was evaluated according to the WHO 2008 protocol of 28-day follow-up and PCR-uncorrected/corrected treatment outcomes were assessed. RESULTS: One hundred and eighty-five children (98 ASAQ and 89 AL) were followed up until day 28. The PCR-corrected ACPR was 98.9% for AS-AQ and 96.4% for AL. Late therapeutic failure rate was 3.6% and 1.1% for AL and AS-AQ, respectively (p = 0.2). Adverse events and serious adverse events were rarely observed with both treatments. CONCLUSION: AS-AQ and AL are still efficacious and well-tolerated for the treatment of uncomplicated malaria in Gabonese children.

Baseline Mapping of Schistosomiasis and Soil Transmitted Helminthiasis in the Northern and Eastern Health Regions of Gabon, Central Africa: Recommendations for Preventive Chemotherapy.

In order to follow the Preventive Chemotherapy (PC) for the transmission control as recommended by WHO, Gabon initiated in 2014 the mapping of Schistosomiasis and Soil Transmitted Helminthiasis (STH). Here, we report the results of the Northern and Eastern health regions, representing a third of the land area and 12% of its total population. All nine departments of the two regions were surveyed and from each, five schools were examined with 50 schoolchildren per school. The parasitological examinations were realized using the filtration method for urine and the Kato-Katz technique for stool samples. Overall 2245 schoolchildren (1116 girls and 1129 boys), mean aged 11.28 ± 0.04 years, were examined. Combined schistosomiasis and STH affected 1270 (56.6%) with variation between regions, departments, and schools. For schistosomiasis, prevalence were 1.7% across the two regions, with no significant difference (p > 0.05) between the Northern (1.5%) and the Eastern (1.9%). Schistosomiasis is mainly caused by Schistosoma haematobium with the exception of one respective case of S. mansoni and S. guineensis. STH are more common than schistosomiasis, with an overall prevalence of 56.1% significantly different between the Northern (58.1%) and Eastern (53.6%) regions (p = 0.034). Trichuris trichiura is the most abundant infection with a prevalence of 43.7% followed by Ascaris lumbricoides 35.6% and hookworms 1.4%. According to these results, an appropriate PC strategy is given. In particular, because of the low efficacy of a single recommended drug on T. trichiura and hookworms, it is important to include two drugs for the treatment of STH in Gabon, due to the high prevalence and intensities of Trichuris infections.

Submicroscopic Falciparum Malaria in Febrile Individuals in Urban and Rural Areas of Gabon.

AbstractCharacterization of the parasite reservoir is required to improve malaria control. Asymptomatic patients with subpatent parasitemia have been identified in Gabon, but the prevalence of such infections among febrile subjects is unclear. We assessed the prevalence of submicroscopic Plasmodium falciparum infections on an island (Port-Gentil), and in urban (Libreville), semiurban (Melen), and rural (Oyem) settings in Gabon. Blood samples (N = 310) from febrile patients were tested for malaria parasites by quantitative nucleic acid sequence-based amplification (QT-NASBA). Parasites were detected in 55.8% (173/310) of samples by microscopy and in 66.4% (206/310) of samples by 18S rRNA QT-NASBA. The proportion of submicroscopic infections differed considerably between sites. Gametocytes were found in 1% (3/310) of the individuals by microscopy and in 32% (99/310) by Pfs25 mRNA QT-NASBA. Thus, submicroscopic parasitemia is frequent in febrile patients, and the detection of this condition is important, to improve disease control.

Genetic Polymorphism of msp1 and msp2 in Plasmodium falciparum Isolates from Côte d'Ivoire versus Gabon.

Introduction. The characterization of genetic profile of Plasmodium isolates from different areas could help in better strategies for malaria elimination. This study aimed to compare P. falciparum diversity in two African countries. Methods. Isolates collected from 100 and 73 falciparum malaria infections in sites of Côte d'Ivoire (West Africa) and Gabon (Central Africa), respectively, were analyzed by a nested PCR amplification of msp1 and msp2 genes. Results. The K1 allelic family was widespread in Côte d'Ivoire (64.6%) and in Gabon (56.6%). For msp2, the 3D7 alleles were more prevalent (>70% in both countries) compared to FC27 alleles. In Côte d'Ivoire, the frequencies of multiple infections with msp1 (45.1%) and msp2 (40.3%) were higher than those found for isolates from Gabon, that is, 30.2% with msp1 and 31.4% with msp2. The overall complexity of infection was 1.66 (SD = 0.79) in Côte d'Ivoire and 1.58 (SD = 0.83) in Gabon. It decreased with age in Côte d'Ivoire in contrast to Gabon. Conclusion. Differences observed in some allelic families and in complexity profile may suggest an impact of epidemiological facies as well as immunological response on genetic variability of P. falciparum.

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177.

Frequencies of dhfr/dhps multiple mutations and Plasmodium falciparum submicroscopic gametocyte carriage in Gabonese pregnant women following IPTp-SP implementation.

This study analyzed the relationship between intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) (IPTp-SP), the rate of multiple resistant parasites and of submicroscopic gametocyte carriage among pregnant women at the beginning of IPTp implementation in Gabon (2005) and six years after (2011). The detection of pfdhfr and pfdhps gene mutations was performed by PCR-RFLP in Plasmodium (P.) falciparum positive samples collected from pregnant women in 2005 and 2011. Gametocytes carriage was detected by Pfs25mRNA amplification using QT-NASBA. Data were analyzed according to the time of collection (study period) and IPTp-SP doses. The proportion of isolates with at least a triple Pfdhfr mutation (n = 39/42, 92.9% versus 100%, n = 78/78)) and of those isolates with the S108N/C59R/N51I/S436A/A437G multiple mutation (17.9% versus 75.6%) significantly increased between 2005 and 2011 (p<0.01). Mutations I164L and A581G were not found, while higher proportions of 436 and 437 mutations were detected in 2011.A trend toward a higher frequency of isolates with five mutations was observed in women who received two SP doses (p<0.01). Pfs25mRNA was found in 6.8 % (n = 3/44) and 34.6% (n = 27/78) of the samples collected in 2005 and 2011 respectively (p<0.01). In 2011, 74.0% (n = 20/27) of women with detected submicroscopic gametocytes carried parasites with the S108N/C59R/N51/S436A/A437G multiple mutation. All the ten delivering women who received three IPTp-SP doses had a submicroscopic Plasmodium falciparum infection, but none had detected gametocytes. Following IPTp-SP implementation, an increase in the frequency of multiple mutant parasites and of submicroscopic gametocyte carriage was observed among pregnant women living in Gabon.

Molecular Detection of Plasmodium falciparum Infection in Matched Peripheral and Placental Blood Samples from Delivering Women in Libreville, Gabon.

Submicroscopic infections account for more than 50% of all Plasmodium (P.) infections in areas with decreasing malaria prevalence and might contribute to poor pregnancy outcomes. The frequency of submicroscopic P. falciparum infections was assessed in matched peripheral and placental blood samples with microscopy negative or discordant results according to IPTp administration. Methods. P. falciparum infection was detected by nested PCR in matched blood samples collected from delivering women with a history of antimalarial drug treatment and living in Gabon. Results. Submicroscopic P. falciparum infections were detected in 87% (n = 33) of the 44 selected matched samples. Plasmodial DNA was found in 90% (n = 35/39) and 87% (n = 33/38) of microscopy negative peripheral and placental blood samples, respectively. Overall, 95% of samples obtained during the high IPTp-SP coverage period had a submicroscopic infection versus 79% among those from the low coverage period. Conclusion. Submicroscopic infections frequency is high in peripheral and placental blood samples from delivering women with a history of antimalarial treatment whatever the level of IPTp coverage. These data highlight the need of accurate diagnostic tools for a regular antenatal screening of malaria during the pregnancy in endemic areas.

Falciparum malaria as an emerging cause of fever in adults living in Gabon, Central Africa.

Following the observed increase of malaria prevalence among older children in Gabon, a descriptive observational study was carried out in 2012 to determine the prevalence of malaria in adults presenting with fever in two health centres of Libreville, the capital city of Gabon. Thick- and thin-blood smears for malaria diagnosis were performed in febrile individuals aged more than 15 years old. Age, use of bed nets, previous antimalarial drug treatment, clinical symptoms, chest radiography results, and available haemoglobin data were also recorded. Among the 304 patients screened, the global malaria frequency was of 42.1% (n = 128/34). Plasmodium (P). falciparum was the only species identified. The proportion of patients with a clinical malaria requiring parenteral treatment was 38.5%, whereas 47.5% of outpatients had uncomplicated malaria. According to WHO classification, 14 (19.7%) infected patients had severe malaria; neurological and respiratory symptoms tended to be more frequent in case of P. falciparum infection. Anaemia was found in 51.5% adults and none had severe anaemia. Almost half of adults consulting for fever in two health centres of the urban city of Libreville have malaria. The use of insecticide-treated bed nets, the screening, and the treatment of individuals with P. falciparum microscopic and submicroscopic asymptomatic infection or clinical malaria should be emphasized to reduce the transmission.

Increase in malaria prevalence and age of at risk population in different areas of Gabon.

BACKGROUND: Following the deployment of new recommendations for malaria control according to the World Health Organization, an estimation of the real burden of the disease is needed to better identify populations at risk and to adapt control strategies. The aim of the present study was to estimate the clinical burden of malaria among febrile children aged less than 11 years, before and after six-year of deployment of malaria control strategies in different areas of Gabon. METHODS: Cross-sectional surveys were carried out in health care facilities at four locations: two urban areas (Libreville and Port-Gentil), one semi-urban area (Melen) and one rural area (Oyem), between 2005 and 2011. Febrile paediatric patients, aged less than 11 years old were screened for malaria using microscopy. Body temperature, history of fever, age, sex, and location were collected. RESULTS: A total of 16,831 febrile children were enrolled; 78.5% (n=13,212) were less than five years old. The rate of Plasmodium falciparum-infection was the lowest in Port-gentil (below 10%) and the highest at Oyem (above 35%). Between 2005 and 2008, malaria prevalence dropped significantly from 31.2% to 18.3%, followed by an increase in 2011 in Libreville (24.1%), Port-Gentil (6.5%) and Oyem (44.2%) (p<0.01). Median age among the infected patients increased throughout the study period reaching 84 (60-108) months in Libreville in 2011 (p<0.01). From 2008, at all sites, children older than five years were more frequently infected; the risk of being infected significantly increased with time, ranging from 0.37 to 1.50 in 2005 and from 2.03 to 5.10 in 2011 in this group (p<0.01). The risk of being P. falciparum-infected in children aged less than five years old significantly decreased from 2008 to 2011 (p<0.01). CONCLUSIONS: This study shows an increased risk of malaria infection in different areas of Gabon with over-five year-old children tending to become the most at-risk population, suggesting a changing epidemiology. Moreover, the heterogeneity of the malaria burden in the country highlights the importance of maintaining various malaria control strategies and redefining their implementation.

A simplified intravenous artesunate regimen for severe malaria.

BACKGROUND: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria. METHODS: This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed. RESULTS: In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008). CONCLUSIONS: Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children. CLINICAL TRIALS REGISTRATION: NCT00522132.

Adolescence as risk factor for adverse pregnancy outcome in Central Africa--a cross-sectional study.

BACKGROUND: Sub-Saharan Africa has the highest rates of maternal and neonatal mortality worldwide. Young maternal age at delivery has been proposed as risk factor for adverse pregnancy outcome, yet there is insufficient data from Sub-Saharan Africa. The present study aimed to investigate the influence of maternal adolescence on pregnancy outcomes in the Central African country Gabon. METHODOLOGY AND PRINCIPAL FINDINGS: Data on maternal age, parity, birth weight, gestational age, maternal Plasmodium falciparum infection, use of bednets, and intake of intermittent preventive treatment of malaria in pregnancy were collected in a cross-sectional survey in 775 women giving birth in three mother-child health centers in Gabon. Adolescent women (≤16 years of age) had a significantly increased risk to deliver a baby with low birth weight in univariable analysis (22.8%, 13/57, vs. 9.3%, 67/718, OR: 2.9, 95% CI: 1.5-5.6) and young maternal age showed a statistically significant association with the risk for low birth weight in multivariable regression analysis after correction for established risk factors (OR: 2.7; 95% CI: 1.1-6.5). In further analysis adolescent women were shown to attend significantly less antenatal care visits than adult mothers (3.3±1.9 versus 4.4±1.9 mean visits, p<0.01, n = 356) and this difference accounted at least for part of the excess risk for low birth weight in adolescents. CONCLUSION: Our data demonstrate the importance of adolescent age as risk factor for adverse pregnancy outcome. Antenatal care programs specifically tailored for the needs of adolescents may be necessary to improve the frequency of antenatal care visits and pregnancy outcomes in this risk group in Central Africa.

Efficacy and safety of a new pediatric artesunate-mefloquine drug formulation for the treatment of uncomplicated falciparum malaria in Gabon.

Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria. The aim of this clinical trial was to evaluate the efficacy, safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation. A total of 71 children aged 1-13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight: 10-20 kg, pediatric group (n = 41); 20-40 kg, tablet group (n = 30). All the children were treated once daily for three days: the pediatric group received the novel granule formulation, the tablet group received the co-blister tablets. The PCR-corrected cure rate on day 28 was evaluated. There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100% in per-protocol analysis. In intention-to-treat analysis the cure rates were 95% in the pediatric group and 97% in the tablet group. The most frequent adverse events were vomiting (17%), abdominal pain (11%) and headache (17%). This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children.

Burden of malaria during pregnancy at the time of IPTp/SP implementation in Gabon.

The new recommendations to prevent malaria in pregnant women have recently been implemented in Gabon. There is little information on the pregnancy indicators that are useful for their evaluation. A cross-sectional study for the assessment of the prevalence of peripheral, placental, and cord malaria and anemia among delivering women was performed at the largest public hospital of Gabon. Malaria prevalence was 34.4%, 53.6%, and 18.2% for maternal peripheral, placental, and cord blood respectively, with no difference between primigravidae and multigravidae. Submicroscopic infections were frequent and concerned all the positive cord samples. Maternal peripheral, late placental, and cord infections were all associated with a reduced mean birth weight in primigravidae (P = 0.02). Anemia prevalence was 53%, low birth rate was 13%, and prematurity was 25%. The use of intermittent preventive treatment with sulfadoxine-pyrimethamine (greater than or equal to one dose) combined with bed net was associated with a reduction in infection only in multigravidae and with a reduced risk of maternal anemia.

Natural killer cell IFN-gamma-activity is associated with Plasmodium falciparum infection during pregnancy.

The ability of natural killer (NK) cells to produce gamma interferon (IFN-gamma) after ex vivo stimulation with crude schizont lysate of Plasmodium falciparum was studied in uninfected and P. falciparum-infected pregnant Gabonese women segregated according to the gravidity at the time of delivery. This activity was measured in purified NK cells as well as in whole blood from the periphery and cord. Crude schizont lysate-stimulated NK cells from primiparous women produced significantly more IFN-gamma than those from multiparous women (P<0.001). Women with malaria infection produced more IFN-gamma than negative women in peripheral blood (P<0.001) indicating that immunological determinants regulating the susceptibility to malaria in pregnant women are parasite-specific. These findings reveal that NK cells are major source of IFN-gamma when exposed to P. falciparum antigens in vitro in absence of any other co-stimulant.