ABSTRACT
BACKGROUND: Schistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants. METHODS: A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time. DISCUSSION: The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines. TRIAL REGISTRATION: The registration number of this study is NCT03779347 ( clinicaltrials.gov , date of registration: 19 December 2018).
Subject(s)
Antigens, Helminth/analysis , Immunologic Tests/methods , Schistosoma haematobium/immunology , Schistosomiasis haematobia/diagnosis , Schistosomiasis haematobia/epidemiology , Animals , Anthelmintics/therapeutic use , Child, Preschool , Cross-Sectional Studies , Data Accuracy , Female , Follow-Up Studies , Gabon/epidemiology , Humans , Infant , Infant, Newborn , Longitudinal Studies , Praziquantel/therapeutic use , Pregnancy , Prevalence , Prospective Studies , Real-Time Polymerase Chain Reaction , Schistosoma haematobium/genetics , Schistosomiasis haematobia/drug therapy , Schistosomiasis haematobia/parasitologyABSTRACT
OBJECTIVE: Tropheryma whipplei, the causative agent of Whipple's disease, can also be identified in stool samples of humans without systemic disease. It is much more frequently detected in human stool samples in tropical environments than in industrialized countries. PCR-screening has been applied for point prevalence studies and environmental assessments in tropical settings, but results depend on the applied assay. We compared one commercial qPCR kit with two well-described in-house assays for detection of T. whipplei from stool. METHODS: Residual materials from nucleic acid extractions of stool samples from two groups with presumably different prevalences and increased likelihood of being colonized or infected by T. whipplei were tested. One group comprised 300 samples from study participants from western Africa (group 1); the second group was of 300 returnees from tropical deployments (group 2). Each sample was assessed with all three qPCR assays. Cycle threshold (Ct ) values were descriptively compared. RESULTS: Based solely on mathematical modeling, the three PCR assays showed considerably different detection rates of T. whipplei DNA in stool samples (kappa 0.67 (95% confidence interval [0.60, 0.73])). Considering the calculated test characteristics, prevalence of 28.3% for group 1 and 5.0% for group 2 was estimated. Discordant test results were associated with later Ct values. The study did not validate the assays for the detection of T. whipplei in Whipple's disease and for diagnostic purposes since clinical specificity and sensitivity were not investigated. CONCLUSIONS: In spite of the observed diagnostic uncertainty, PCR-based screening approaches can be used for epidemiological purposes and environmental samples to define the source and reservoir in resource-limited tropical settings if prevalence is calculated using diagnostic accuracy-adjusted methods.
Subject(s)
DNA, Bacterial/isolation & purification , Feces/microbiology , Real-Time Polymerase Chain Reaction , Whipple Disease/diagnosis , Whipple Disease/microbiology , Adult , Bacteriological Techniques , Humans , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
Schistosomiasis is a common disease in endemic areas of Sub-Saharan Africa, South America and Asia. It is rare in Europe, mainly imported from endemic countries due to travelling or human migration. Available methods for the diagnosis of schistosomiasis comprise microscopic, molecular and serological approaches, with the latter detecting antigens or antibodies associated with Schistosoma spp. infection. The serological approach is a valuable screening tool in low-endemicity settings and for travel medicine, though the interpretation of any diagnostic results requires knowledge of test characteristics and a patient's history. Specific antibody detection by most currently used assays is only possible in a relatively late stage of infection and does not allow for the differentiation of acute from previous infections for therapeutic control or the discrimination between persisting infection and re-infection. Throughout the last decades, new target antigens have been identified, and assays with improved performance and suitability for use in the field have been developed. For numerous assays, large-scale studies are still required to reliably characterise assay characteristics alone and in association with other available methods for the diagnosis of schistosomiasis. Apart from S. mansoni, S. haematobium and S. japonicum, for which most available tests were developed, other species of Schistosoma that occur less frequently need to be taken into account. This narrative review describes and critically discusses the results of published studies on the evaluation of serological assays that detect antibodies against different Schistosoma species of humans. It provides insights into the diagnostic performance and an overview of available assays and their suitability for large-scale use or individual diagnosis, and thus sets the scene for serological diagnosis of schistosomiasis and the interpretation of results.
Subject(s)
Schistosomiasis/blood , Schistosomiasis/diagnosis , Serotyping/methods , Animals , Antibodies, Helminth/immunology , Antigens, Helminth/immunology , Humans , Schistosoma/immunology , Schistosoma/physiology , Schistosomiasis/immunologyABSTRACT
BACKGROUND: Staphylococcus aureus is among the most common pathogens isolated from blood cultures in Ghana; yet the epidemiology of blood infections in rural settings is poorly described. This study aims to investigate antimicrobial susceptibility and clonal diversity of S. aureus causing bloodstream infections in two hospitals in the Ashanti Region, Ghana. METHODS: Blood cultures were performed for all febrile patients (≥37.5 °C) on hospital admission. Antibiotic susceptibility testing for S. aureus isolates was carried out by the VITEK 2 system. Multiplex polymerase chain reaction (PCR) was used to detect S. aureus-specific nuc gene, Panton-Valentine leukocidin (PVL), and methicillin-resistant S. aureus (MRSA)-specific mecA and mecC genes. The population structure of S. aureus was assessed by spa typing. RESULTS: In total, 9,834 blood samples were cultured, out of which 0.6% (n = 56) were positive for S. aureus. Multidrug resistance (MDR) was detected in 35.7% (n = 20) of the S. aureus strains, of which one was a MRSA. The highest rate of antibiotic resistance was seen for commonly available antibiotics, including penicillin (n = 55; 98.2%), tetracycline (n = 32; 57.1%) and trimethoprim/sulfamethoxazole (n = 26; 46.4%). Of all S. aureus strains, 75.0% (n = 42) carried the PVL-encoding genes. We found 25 different spa types with t355 (n = 11; 19.6%), t314 (n = 8; 14.3%), t084 (n = 8; 14.3%) and t311 (n = 5; 8.9%) being predominant. CONCLUSION: The study exhibited an alarmingly large level of antibiotic resistance to locally available antibiotics. The frequency of genetically diverse and PVL-positive methicillin-sensitive S. aureus (MSSA) was high and could represent a reservoir for the emergence of virulent PVL-positive MRSA clones.
Subject(s)
Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Adolescent , Bacteremia/microbiology , Bacterial Proteins/genetics , Bacterial Toxins/genetics , Child , Child, Preschool , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/genetics , Exotoxins/genetics , Female , Genetic Variation , Ghana , Hospitals , Humans , Infant , Infant, Newborn , Leukocidins/genetics , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Multiplex Polymerase Chain Reaction , Penicillin-Binding Proteins/genetics , Rural Population , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicityABSTRACT
BACKGROUND: Malaria epidemiology in Madagascar is classified into four different areas, ranging from unstable seasonal transmission in the highlands to hyperendemic perennial transmission areas in the costal level. Most malaria studies in Madagascar are focused on symptomatic children. However, because of the low transmission in some areas with correspondingly low level of semi-immunity, adults are also at risk, in particular pregnant women. The objective of this study was to gain information on the genetic epidemiology of malarial infections in pregnant women in order to provide information for malaria control and elimination programmes in Madagascar. METHODS: Between May and August 2010, we carried out cross-sectional surveys targeting healthy pregnant women in six locations, three in the coastal area and three in the highlands at 850-1300 m. 1244 blood samples were screened for anti-Plasmodium falciparum antibodies by immunofluorescence test and for malarial infection by realtime-PCR. The prevalence of chloroquine and sulphadoxine-pyrimethamine resistance markers was also determined in all Plasmodium falciparum samples by PCR-RFLP as well as the multiplicity of infection through genotyping six neutral microsatellites. RESULTS: In the highlands, 67.4% of the women presented antibodies against Plasmodium falciparum and 9.2% were carrying parasites, at the coast 95.6% and 14.8%, respectively. In the mean, 1.2 clones were detected in infected pregnant woman in the highlands and 1.5 at the coast. A higher level of monoclonal infections was found in the highlands (85.4%) compared to the coast (61.8%). Resistance markers for sulphadoxine-pyrimethamine were present only in two sites. CONCLUSION: Immunity is triggered in Malagasy highland populations when they are infected with malaria parasites, but these populations could also serve as a reservoir for epidemics.
Subject(s)
Antimalarials/pharmacology , Asymptomatic Infections/epidemiology , Drug Resistance , Malaria/epidemiology , Malaria/parasitology , Plasmodium/drug effects , Plasmodium/genetics , Adolescent , Adult , Antibodies, Protozoan , Chloroquine/pharmacology , Drug Combinations , Female , Fluorescent Antibody Technique, Indirect , Humans , Madagascar/epidemiology , Middle Aged , Molecular Epidemiology , Pregnancy , Prevalence , Protozoan Proteins/genetics , Pyrimethamine/pharmacology , Real-Time Polymerase Chain Reaction , Seroepidemiologic Studies , Sulfadoxine/pharmacology , Young AdultABSTRACT
BACKGROUND: Salmonella enterica is an important cause of diarrhea with the potential to cause systemic infection including sepsis, particularly in the tropics. Sepsis in particular requires quick and reliable identification to allow a rapid optimization of antibiotic therapy. We describe the establishment and evaluation of fluorescence in situ hybridization (FISH) as a rapid and easy-to-perform molecular identification procedure from agar and blood culture broths. METHODS: Two newly developed FISH probes with specificity for Salmonella spp. were evaluated with 10 reference strains, 448 clinical isolates of Gram-negative bacteria from Germany and Ghana including 316 Salmonella spp. strains, and 39 environmental Salmonella spp. isolates from rivers and streams in Ghana. One FISH probe was further tested with 207 pre-incubated blood culture broths from Germany with Gram-negative rod-shaped bacteria in Gram stain. RESULTS: Evaluation of the newly designed FISH probes demonstrated sensitivity of 99.2% and specificity of 98.4% for clinical isolates, sensitivity of 97.4% for environmental Salmonella spp. isolates, and sensitivity of 100% and specificity of 99.5% for blood culture materials. CONCLUSIONS: FISH proved to be highly reliable for a rapid identification of Salmonella spp. directly from pre-incubated blood culture broths as well as after growth on agar. The inexpensive and easy-to-perform procedure is particularly suitable for resource-limited areas where more sophisticated procedures are not available.
Subject(s)
Bacteriological Techniques/methods , In Situ Hybridization, Fluorescence/methods , Molecular Diagnostic Techniques/methods , Salmonella Infections/diagnosis , Salmonella/classification , Salmonella/isolation & purification , Animals , Germany , Ghana , Humans , Oligonucleotide Probes/genetics , Salmonella/genetics , Sensitivity and SpecificityABSTRACT
OBJECTIVES: Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow-up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. METHODS: Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow-up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. RESULTS: Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. CONCLUSIONS: Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.
Subject(s)
HIV Infections/epidemiology , HIV , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/epidemiology , Syphilis/epidemiology , Treponema pallidum , Adolescent , Adult , Child , Female , HIV Infections/blood , HIV Infections/diagnosis , HIV Infections/microbiology , Health Services Needs and Demand , Humans , Madagascar/epidemiology , Mass Screening , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/microbiology , Prevalence , Retrospective Studies , Rural Population , Seroepidemiologic Studies , Syphilis/blood , Syphilis/diagnosis , Syphilis/microbiology , Syphilis Serodiagnosis , Young AdultABSTRACT
BACKGROUND: Invasive enteropathogenic bacteria can cause systemic infections. Data from studies with PCR detection suggest, at least for Salmonella enterica, that blood culture may lead to underestimation in the tropics. Corresponding data are lacking for other invasive enteropathogenic bacteria. We compared classical blood culture and molecular methods for the diagnosis of blood infections. METHODS: A real-time multiplex PCR for Salmonella spp., Shigella spp./entero- invasive Escherichia coli (EIEC), Yersinia spp., and Campylobacter jejuni was applied to 2321 retained blood culture samples from Ghanaian patients, after enrichment by automated culture. RESULTS: PCR detected Salmonella DNA in 56 out of 58 pre-incubated Ghanaian blood cultures with growth of S. enterica. In 2 samples molecular diagnosis was only possible after 1:10 dilution. Twenty-two samples negative by blood culture and 1 positive with Micrococcus spp. were PCR-positive for Salmonella spp. In addition, 3 Shigella spp./EIEC, 2 Yersinia spp., and 1 C. jejuni were detected by PCR but not by culture growth. CONCLUSIONS: Real-time PCR was more sensitive in identifying invasive enteropathogenic bacteria than automated blood culture, which is hampered by a lack of evidence-based standardization of pre-analytic conditions in the tropics. Primary agar culture and Gram-staining prior to automated blood culture is advisable in cases where transportation times are long.
Subject(s)
Bacteremia/diagnosis , Bacteriological Techniques/methods , Blood/microbiology , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae/isolation & purification , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction/methods , Adult , Bacteremia/microbiology , Child , Child, Preschool , Enterobacteriaceae Infections/microbiology , Ghana , Humans , Multiplex Polymerase Chain Reaction/methods , Sensitivity and SpecificityABSTRACT
In October 2009, two-3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450-1,300 m high, IgG seroprevalence against CHIKV was 0%-3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission.
Subject(s)
Antibodies, Viral/immunology , Chikungunya virus/immunology , Dengue Virus/immunology , Fever/epidemiology , Fever/immunology , Rift Valley fever virus/immunology , Animals , Antibodies, Viral/blood , Antibody Specificity/immunology , Cell Line , Disease Outbreaks , Fever/virology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Madagascar/epidemiology , Seroepidemiologic StudiesABSTRACT
BACKGROUND: In malarious areas of the world, a higher proportion of the population has blood group O than in non-malarious areas. This is probably due to a survival advantage conferred either by an attenuating effect on the course of or reduction in the risk of infection by plasmodial parasites. Here, the association between ABO blood group and incidence of placental malaria was assessed in order to determine the possible influence of the former on the latter. METHODS: Data from a study in Lambaréné, Gabon, and data from three previously published reports of studies in The Gambia, Malawi and Sudan, were compiled and compared. ABO blood groups were cross-tabulated with placental malaria stratified by parity. Odds ratios (OR), stratified by parity, were calculated for the outcome, placental parasitaemia, and compared between blood group O vs. non-O mothers in all four studies. Random effects meta-analysis of data from individual studies from areas with perennial hyper/holoendemic transmission was performed. RESULTS: In Gabon, the odds ratio (OR) for active placental parasitaemia in mothers with group O was 0.3 (95% CI 0.05-1.8) for primiparae and 0.7 (95% CI 0.3-1.8) for multiparae. The OR for primiparae in the published study from The Gambia was 3.0 (95% CI 1.2-7.3) and, in Malawi, 2.2 (95% CI 1.1-4.3). In the Sudanese study, no OR for primiparae could be calculated. The OR for placental parasitaemia in group O multiparae was 0.8 (95% CI 0.3-1.7) in the Gambia, 0.6 (95% CI 0.4-1.0) in Malawi and 0.4 (95% CI 0.1-1.8) in Sudan. Combining data from the three studies conducted in hyper-/holo-endemic settings (Gambia, Malawi, Gabon) the OR for placental malaria in blood group O multiparae was 0.65 (95% CI 0.44-0.96) and for primiparae 1.70 (95% CI 0.67-4.33). CONCLUSION: Studies conducted in The Gambia and Malawi suggest that blood group O confers a higher risk of active placental infection in primiparae, but a significantly lower risk in multiparae. These findings were not confirmed by the study from Gabon, in which statistically non-significant trends for reduced risk of placental parasitaemia in those with blood group O, regardless of parity, were observed.
Subject(s)
ABO Blood-Group System , Malaria/epidemiology , Placenta Diseases/epidemiology , Adult , Africa South of the Sahara/epidemiology , Female , Humans , Incidence , Models, Statistical , Placenta/parasitology , Placenta/pathology , Pregnancy , Risk AssessmentABSTRACT
BACKGROUND: The diagnosis and antimicrobial treatment of pneumonia in African children in the absence of diagnostic means such as x-ray facilities or microbiological laboratories relies primarily on clinical symptoms presented by the patients. In order to assess the spectrum of bacterial pathogens, blood cultures were performed in children fulfilling the clinical criteria of pneumonia. METHODS: In total, 1032 blood cultures were taken from children between 2 months and 5 years of age who were admitted to a rural hospital in Ghana between September 2007 and July 2009. Pneumonia was diagnosed clinically and according to WHO criteria classified as "non-severe pneumonia" and "severe pneumonia" ("severe pneumonia" includes the WHO categories "severe pneumonia" and "very severe pneumonia"). RESULTS: The proportion of bacteriaemia with non-typhoid salmonella (NTS) was similar in children with pneumonia (16/173, 9.2%) compared to children hospitalized for other reasons (112/859, 13%). NTS were the predominant organisms isolated from children with clinical pneumonia and significantly more frequent than Streptococcus pneumoniae (8/173, 4.6%). Nine percent (9/101) of children presenting with severe pneumonia and 10% (7/72) of children with non-severe pneumonia were infected with NTS. Nineteen out of 123 NTS isolates (15%) were susceptible to aminopenicillins (amoxycillin/ampicillin), 23/127 (18%) to chlorampenicol, and 23/98 (23%) to co-trimoxazole. All NTS isolates were sensitive to ceftriaxone and ciprofloxacin. CONCLUSION: In Sub-saharan Africa, sepsis with NTS should be considered in children with symptoms of pneumonia and aminopenicillins might often not be the adequate drugs for treatment.
Subject(s)
Bacteremia/epidemiology , Pneumonia/epidemiology , Salmonella Infections/epidemiology , Salmonella/isolation & purification , Bacteremia/blood , Bacteremia/microbiology , Child, Preschool , Drug Resistance, Bacterial , Ghana , Humans , Infant , Microbial Sensitivity Tests , Pneumonia/blood , Pneumonia/microbiology , Salmonella/drug effects , Salmonella Infections/blood , Salmonella Infections/microbiologyABSTRACT
In the context of a trial studying intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Lambaréné, Gabon, children aged 18-30 months were followed up after having received their last dose at an age of 15 months. In the intention-to-treat population, the protective efficacy against all malaria episodes was -18.0 (95% confidence interval, -97.4 to 29.5; P = .529). The protective efficacy against first or only anemia episode was -45.3 (95% confidence interval, -234.5 to 36.3; P=.375). The protective efficacies were negative and were not statistically significant. These results do not appear to support the concept of a rebound effect after intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants. Clinical trials registration. NCT00167843.
Subject(s)
Antimalarials/therapeutic use , Malaria/prevention & control , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Anemia/epidemiology , Anemia/prevention & control , Child, Preschool , Cohort Studies , Double-Blind Method , Drug Administration Schedule , Drug Combinations , Gabon/epidemiology , Humans , Infant , Kaplan-Meier Estimate , Malaria/drug therapy , Malaria/epidemiology , MorbidityABSTRACT
Schistosoma antigen detection tests have a large potential for schistosomiasis control programs due to their ability to detect active and ongoing Schistosoma infections, their much higher sensitivity compared to microscopical methods, and the possibility to use non-invasive urine samples. Pregnant women and young children could especially benefit from affordable and easy-to-use antigen tests as inclusion of these vulnerable groups in mass drug administration campaigns will always require higher justification hurdles, especially in low to middle endemic regions with a higher proportion of individuals who are not infected and thus unnecessarily exposed to praziquantel. The overall objective of the 'fast and reliable easy-to-use diagnostics for eliminating bilharzia in young children and mothers' (freeBILy, www.freeBILy.eu) project is to thoroughly evaluate the point-of-care circulating cathodic antigen (POC-CCA) and the up-converting phosphor reporter particle, lateral flow circulating anodic antigen (UCP-LF CAA) urine strip tests to diagnose Schistosoma infections in pregnant women and young children and to assess their potential as a schistosomiasis control tool in test-and-treat strategies. The freeBILy project will generate valuable, evidence-based findings on improved tools and test-and-treat strategies to reduce the burden of schistosomiasis in pregnant women and young children.
Subject(s)
Anthelmintics/therapeutic use , Antigens, Helminth/isolation & purification , Praziquantel/therapeutic use , Schistosoma/isolation & purification , Schistosomiasis/drug therapy , Adult , Animals , Antigens, Helminth/immunology , Child , Child, Preschool , Female , Humans , Immunologic Tests , Longitudinal Studies , Male , Mothers , Point-of-Care Systems , Pregnancy , Schistosomiasis/epidemiology , Sensitivity and SpecificityABSTRACT
BACKGROUND: Two commercial PCR assays were assessed in a retrospective study to determine their reliability as tools for the differentiation of Plasmodium species in human blood. METHODS: A total of 1022 blood samples from 817 patients with suspected or confirmed malaria submitted to the German National Reference Centre for Tropical Pathogens were subjected to malaria microscopy using thick and thin blood films as well as to a genus-specific malaria real-time PCR. Parasite-positive samples were analysed by RealStar Malaria S&T PCR Kit 1.0 (altona Diagnostics) and FTD Malaria Differentiation (Fast Track Diagnostics) multiplex real-time PCR assays targeting species-specific Plasmodium DNA. RESULTS: Out of the 1022 blood samples, 247 (24.2%) tested positive for Plasmodium spp. The two multiplex assays showed rather similar performance characteristics and provided concordant species information in 98.9% of samples positive by malaria microscopy and in 95.1% (RealStar) and 96.8% (FTD) of samples positive by genus-specific PCR. Compared to FTD, RealStar revealed slightly reduced sensitivity for submicroscopic, low-level P. falciparum infections, while FTD was unable to detect P. knowlesi. CONCLUSIONS: The two commercial malaria PCR assays assessed are suitable for discriminating Plasmodium species in clinical samples, and can provide additional information in cases of microscopically uncertain findings.
Subject(s)
Malaria/diagnosis , Malaria/parasitology , Molecular Typing/methods , Multiplex Polymerase Chain Reaction/standards , Humans , Species SpecificityABSTRACT
BACKGROUND: Plasmodium falciparum infection during pregnancy is associated with stillbirth, fetal growth restriction, and low birth weight. An additional consequence may be increased risk of malaria in early life, although the epidemiological evidence of this consequence is limited. METHODS: A cohort of 527 children were observed actively every month for 30 months after delivery. Offspring of mothers with microscopically detectable placental P. falciparum infection at the time of delivery were defined as exposed. The outcome measure was malaria (parasitemia and fever). Analyses were performed using Cox proportional hazard models and were stratified by gravidity. RESULTS: Overall, offspring of mothers with placental P. falciparum infection had a significantly higher risk of clinical malaria during the first 30 months of life (adjusted hazard ratio, 2.1; 95% confidence interval [CI], 1.2-3.7). The adjusted hazard ratio for offspring of multigravidae was 2.6 (95% CI, 1.3-5.3), and that for primigravidae was 1.5 (95% CI, 0.6-3.8). The offspring of placenta-infected primigravidae had no episodes of malaria during the first year of life. CONCLUSIONS: Our findings show that active placental P. falciparum infection detected at delivery is associated with an approximately 2-fold greater risk of malaria during early life, compared with noninfection. The fact that persons born to infected multigravidae rather than primigravidae appear to be at greater risk emphasizes the importance of preventing malaria in mothers of all gravidities.
Subject(s)
Malaria/epidemiology , Placenta Diseases/parasitology , Plasmodium falciparum/isolation & purification , Pregnancy Complications, Parasitic , Adult , Animals , Child, Preschool , Cohort Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Longitudinal Studies , Male , Pregnancy , Proportional Hazards Models , RiskABSTRACT
BACKGROUND: Insecticide-treated bed nets (ITNs) range among the most effective measures of malaria prophylaxis, yet their implementation level in sub-Saharan Africa is still low. The goal of this study was to investigate the influence of socio-economic factors on the use of bed nets by mothers in Gabon. METHODS: A cross-sectional study was conducted completing pre-tested, interviewer-administered questionnaires exploring socioeconomic proxy measures with 397 mothers or guardians of young children. Respondents were grouped according to their socio-economic situation, using scores. The condition of the bed nets was evaluated during a home visit. RESULTS: Socio-economic factors of wellbeing were negatively associated with bed net use, such as living in a stone house (OR 0.26, 95% CI 0.14-0.48), running water in the house (OR 0.44, 95% CI 0.21-0.92), shower/flush toilet in the house (OR 0.39/0.34, 95% CI 0.21-0.75/0.16-0.73), ownership of a freezer (OR 0.50, 95% CI 0.26-0.96) and belonging to the highest group in the economic score (OR 0.32, 95% CI 0.15-0.67). In contrast, similar factors were positively associated with a good maintenance condition of the bed nets: higher monthly income (OR 5.64, 95% CI 2.41-13.19) and belonging to the highest group in the economic score (OR 2.55, 95% CI 1.19 - 5.45). CONCLUSION: Among the poorest families in Lambaréné the coverage with untreated nets (UTNs) is the highest, but the condition of these UTNs is the worst. To achieve a broad implementation of ITNs in Lambaréné, there is an urgent need for educational programmes as well as need-tailored marketing strategies for ITNs.
Subject(s)
Malaria/epidemiology , Malaria/prevention & control , Mosquito Control/methods , Child, Preschool , Cross-Sectional Studies , Female , Gabon/epidemiology , Humans , Infant , Legal Guardians , Mothers , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. METHODS: Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. RESULTS: Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. CONCLUSION: The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. TRIAL REGISTRATION: Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambaréné Trial), http://www.clinicaltrials.gov.
Subject(s)
Antimalarials/administration & dosage , Malaria, Falciparum/drug therapy , Malaria, Falciparum/prevention & control , Pyrimethamine/administration & dosage , Sulfadoxine/administration & dosage , Drug Administration Schedule , Drug Combinations , Gabon , Ghana , Humans , Infant , Regression Analysis , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Artesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs) recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce. METHODS: The effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32), compared with the efficacy when given under full supervision (n = 29) to children with falciparum malaria were assessed in an unrandomized study. RESULTS: 61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69-95 %) in the supervised group and 63 % (20 of 32 patients; CI 45-77 %) in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04). No severe adverse events were reported. CONCLUSION: The effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation.
Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Sesquiterpenes/therapeutic use , Amodiaquine/administration & dosage , Amodiaquine/adverse effects , Animals , Antimalarials/administration & dosage , Antimalarials/adverse effects , Artemisinins/administration & dosage , Artemisinins/adverse effects , Artesunate , Child, Preschool , Drug Therapy, Combination , Gabon , Humans , Infant , Malaria, Falciparum/parasitology , Sesquiterpenes/administration & dosage , Sesquiterpenes/adverse effects , Treatment OutcomeSubject(s)
Typhoid Fever/epidemiology , Adolescent , Child , Child, Preschool , Ghana/epidemiology , Humans , Infant , Infant, NewbornABSTRACT
Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné, Gabon, and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines. A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily. Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day quinine regimen was 60% (95% confidence interval: 46-72%). We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed.