Sleep apnea in patients undergoing coronary artery bypass grafting: Impact on perioperative outcomes.

Sleep-disordered breathing is common in patients with coronary artery disease undergoing coronary artery bypass grafting. Sleep-disordered breathing is associated with increased perioperative morbidity, arrhythmias (e.g. atrial fibrillation) and mortality. This study investigated the impact of sleep-disordered breathing on the postoperative course after coronary artery bypass grafting, including development of atrial fibrillation. This prospective single-centre cohort study included adults undergoing coronary artery bypass grafting. All were screened for sleep-disordered breathing (polygraphy) and atrial fibrillation (electrocardiogram) preoperatively; those with known sleep-disordered breathing or atrial fibrillation were excluded. Endpoints included new-onset atrial fibrillation, duration of mechanical ventilation, time in the intensive care unit, and postoperative infection. Regression analysis was performed to identify associations between sleep-disordered breathing and these outcomes. A total of 508 participants were included (80% male, median age 68 years). The prevalence of any (apnea-hypopnea index ≥ 5 per hr), moderate (apnea-hypopnea index = 15-30 per hr) and severe (apnea-hypopnea index > 30 per hr) sleep-disordered breathing was 52.9%, 9.3% and 10.2%, respectively. All-cause 30-day mortality was 0.98%. After adjustment for age and sex, severe sleep-disordered breathing was associated with longer respiratory ventilation support (crude odds ratio [95% confidence interval] 5.28 [2.18-12.77]; p < 0.001) and higher postoperative infection rates (crude odds ratio 3.32 [1.45-7.58]; p < 0.005), but not new-onset atrial fibrillation or mortality. New-onset atrial fibrillation was significantly associated with postoperative infection and prolonged hospital stay. The significant associations between sleep-disordered breathing and several adverse outcomes after coronary artery bypass grafting support the need for preoperative sleep-disordered breathing screening in individuals undergoing cardiac surgery.

Challenges in the clinical development pathway for triple and multiple drug combinations in the treatment of uncomplicated falciparum malaria.

The addition of a third anti-malarial drug matching the pharmacokinetic characteristics of the slowly eliminated partner drug in artemisinin-based combination therapy (ACT) has been proposed as new therapeutic paradigm for the treatment of uncomplicated falciparum malaria. These triple artemisinin-based combination therapy (TACT) should in theory more effectively prevent the development and spread of multidrug resistance than current ACT. Several clinical trials evaluating TACT-or other multidrug anti-malarial combination therapy (MDACT)-have been reported and more are underway. From a regulatory perspective, these clinical development programmes face a strategic dilemma: pivotal clinical trials evaluating TACT are designed to test for non-inferiority of efficacy compared to standard ACT as primary endpoint. While meeting the endpoint of non-inferior efficacy, TACT are consistently associated with a slightly higher frequency of adverse drug reactions than currently used ACT. Moreover, the prevention of the selection of specific drug resistance-one of the main reasons for TACT development-is beyond the scope of even large-scale clinical trials. This raises important questions: if equal efficacy is combined with poorer tolerability, how can then the actual benefit of these drug combinations be demonstrated? How should clinical development plans be conceived to provide objective evidence for or against an improved management of patients and effective prevention of anti-malarial drug resistance by TACT? What are the objective criteria to ultimately convince regulators to approve these new products? In this Opinion paper, the authors discuss the challenges for the clinical development of triple and multidrug anti-malarial combination therapies and the hard choices that need to be taken in the further clinical evaluation and future implementation of this new treatment paradigm.

Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers.

The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.

Predictive Performance of Rapid Diagnostic Tests for Falciparum Malaria and Its Modeled Impact on Integrated Community Case Management of Malaria in Sub-Saharan African Febrile Children.

BACKGROUND: Integrated community case management (iCCM) of malaria complements public health services to improve access to timely diagnosis and treatment of malaria. ICCM relies on standardized test-and-treat algorithms implemented by community health workers using malaria rapid diagnostic tests (RDTs). However, due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria. In this study, we modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria. METHODS: Positive predictive values (PPVs) and negative predictive values (NPVs) of RDTs for clinical malaria were modeled. Assay-specific performance characteristics stem from the Cochrane Library and data on the proportion of malaria-attributable fevers among African febrile children aged <5 years were used as prevalence matrix. RESULTS: Average country-level PPVs vary considerably. Ethiopia had the lowest PPVs (histidine-rich protein II [HRP2] assay, 17.35%; parasite lactate dehydrogenase [pLDH] assay, 39.73%), and Guinea had the highest PPVs (HRP2 assay, 95.32%; pLDH assay, 98.46%). On the contrary, NPVs were above 90% in all countries (HRP2 assay, ≥94.87%; pLDH assay, ≥93.36%). CONCLUSIONS: PPVs differed considerably within Africa when used to screen febrile children, indicating unfavorable performance of RDT-based test-and-treat algorithms in low-PPV settings. This suggests that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings. Therefore, current iCCM algorithms should be complemented by information on other setting-specific major causes of fever.

Prospective Clinical and Molecular Evaluation of Potential Plasmodium ovale curtisi and wallikeri Relapses in a High-transmission Setting.

BACKGROUND: Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this prospective study was to characterize the reappearance patterns of ovale parasites. METHODS: P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria. RESULTS: At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi. CONCLUSION: These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.

Use of Capillary Blood Samples Leads to Higher Parasitemia Estimates and Higher Diagnostic Sensitivity of Microscopic and Molecular Diagnostics of Malaria Than Venous Blood Samples.

Background: Diagnosis of malaria is usually based on samples of peripheral blood. However, it is unclear whether capillary (CAP) or venous (VEN) blood samples provide better diagnostic performance. Quantitative differences of parasitemia between CAP and VEN blood and diagnostic performance characteristics were investigated. Methods: Patients were recruited between September 2015 and February 2016 in Gabon. Light microscopy and quantitative polymerase chain reaction (qPCR) measured parasitemia of paired CAP and VEN samples. CAP and VEN performance characteristics using microscopy were evaluated against a qPCR gold standard. Results: Microscopy revealed a median parasitemia of 495/µL in CAP and 429/µL in VEN samples, manifesting in a 16.6% (P = .04) higher CAP parasitemia compared with VEN parasitemia. Concordantly, in qPCR -0.278 (P = .006) cycles were required for signal detection in CAP samples. CAP sensitivity of microscopy relative to the gold standard was 81.5% vs VEN sensitivity of 73.4%, while specificities were 91%. CAP and VEN sensitivities dropped to 63.3% and 45.9%, respectively, for a subpopulation of low-level parasitemias, whereas specificities were 92%. Conclusions: CAP sampling leads to higher parasitemias compared to VEN sampling and improves diagnostic sensitivity. These findings may have important implications for routine diagnostics, research, and elimination campaigns of malaria.

Efficacy and Safety of Fosmidomycin-Piperaquine as Nonartemisinin-Based Combination Therapy for Uncomplicated Falciparum Malaria: A Single-Arm, Age De-escalation Proof-of-Concept Study in Gabon.

Background: Fosmidomycin-piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. Methods: The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150000/µL received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)-corrected day 28 adequate clinical and parasitological response (ACPR). Results: One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96-100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6-60) and fever clearance time (median, 12 hours; IQR, 6-48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. Conclusions: This is the first report of the use of the combination fosmidomycin-piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval. Clinical Trials Registration. NCT02198807.

Leishmaniasis in Northern Syria during Civil War.

Since the onset of the ongoing civil war in Syria, the governmental surveillance system for leishmaniasis has lost access to provinces of northern Syria. The MENTOR Initiative, an international not-for-profit organization, was commissioned to implement an integrated leishmaniasis control program, providing an opportunity to reassess the epidemiology of leishmaniasis in northern Syria. Epidemiologic data and biologic samples for molecular species diagnostics were collected from collaborating local health centers. Incidence peaked in March 2015 at 7,743 estimated monthly cases. High levels of transmission were observed in traditional endemic regions but extended to previously hypoendemic regions, such as Al-Raqqa and Al-Hasakah. Incidence decreased to 3,209 in July 2015. Data indicate that the prewar trend of increasing incidence of cutaneous leishmaniasis accelerated during the beginning of armed conflict but declined after implementation of the comprehensive control program by the MENTOR Initiative. Molecular analysis revealed a spectrum of Leishmania species and sporadic cases of visceral leishmaniasis.

Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium malariae, Plasmodium ovale, and Mixed Plasmodium Malaria in Gabon.

Treatment recommendations for Plasmodium malariae and Plasmodium ovale malaria are largely based on anecdotal evidence. The aim of this prospective study, conducted in Gabon, was to systematically assess the efficacy and safety of artemether-lumefantrine for the treatment of patients with uncomplicated P. malariae or P. ovale species monoinfections or mixed Plasmodium infections. Patients with microscopically confirmed P. malariae, P. ovale, or mixed-species malaria with at least one of these two Plasmodium species were treated with an oral, fixed-dose combination of artemether-lumefantrine for 3 consecutive days. The primary endpoints were per-protocol PCR-corrected adequate clinical and parasitological response (ACPR) on days 28 and 42. Tolerability and safety were recorded throughout the follow-up period. Seventy-two participants (42 male and 30 female) were enrolled; 62.5% of them had PCR-corrected mixed Plasmodium infections. Per protocol, PCR-corrected ACPR rates were 96.6% (95% confidence interval [CI], 91.9 to 100) on day 28 and 94.2% (95% CI, 87.7 to 100) on day 42. Considering Plasmodium species independently from their coinfecting species, day 42 ACPR rates were 95.5% (95% CI, 89.0 to 100) for P. falciparum, 100% (exact CI, 84.6 to 100) for P. malariae, 100% (exact CI, 76.8 to 100) for P. ovale curtisi, and 90.9% (95% CI, 70.7 to 100) for P. ovale wallikeri Study drug-related adverse events were generally mild or moderate. In conclusion, this clinical trial demonstrated satisfying antimalarial activity of artemether-lumefantrine against P. ovalewallikeri, P. ovale curtisi, P. malariae, and mixed Plasmodium infections, with per-protocol efficacies of 90% to 100% and without evident tolerability or safety concerns. (This trial was registered in the clinical study database ClinicalTrials.gov under the identifier NCT02528279.).

Validity and reliability of methods to microscopically detect and quantify malaria parasitaemia.

OBJECTIVES: The recommended microscopy method by WHO to quantify malaria parasitaemia yields inaccurate results when individual leucocyte (WBC) counts deviate from 8000 leucocytes/µl. A method avoiding WBC count assumptions is the Lambaréné method (LAMBA). Thus, this study compared validity and reliability of the LAMBA and the WHO method. METHODS: Three methods for counting parasitaemia were applied in parallel in a blinded assessment: the LAMBA, the WHO method using a standard factor of 8000 leucocytes/µl ['simple WHO method' (sWHO)] and the WHO method using measured WBC counts ['accurate WHO method' (aWHO)]. Validity was assessed by comparing LAMBA and sWHO to the gold standard measurement of aWHO. Reliability was ascertained by computation of intraclass correlation coefficients (ICCs). RESULTS: 787 malaria-positive thick smears were analysed. Parasitaemia as determined by LAMBA and sWHO increasingly deviated from aWHO the more patients' WBCs diverged from 8000/µl. Equations of linear regression models assessing method deviation in percent from gold standard as function of WBC count were y = -0.00608x (95% CI -0.00693 to -0.00524) + 47.8 for LAMBA and y = -0.0125x (95% CI -0.01253 to -0.01247) + 100.1 for sWHO. Comparison of regression slopes showed that the deviation was twice as high for sWHO as for LAMBA (P < 0.001). ICCs were excellent (>90%) for both methods. CONCLUSIONS: The LAMBA has higher validity than the sWHO and may therefore be preferable in resource-limited settings without access to routine WBC-evaluation.

Human Placental Schistosomiasis-A Systematic Review of the Literature.

BACKGROUND: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on PS. METHODS: We conducted a systematic literature search on PubMed, EMBASE, and Medline and included all publications that reported microscopically confirmed cases of PS, as well as the relevant secondary literature found in the citations of the primarily included publications. RESULTS: Out of 113 abstracts screened we found a total of 8 publications describing PS with a total of 92 cases describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association with adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only <1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. CONCLUSIONS: PS is a highly unattended and underdiagnosed condition in endemic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

Evaluation of knowledge, attitude and practice towards loiasis in the rural community of Sindara, in central African Gabon.

BACKGROUND: More than 20 million people are infected with L. loa, and around 40 million live in high or intermediate-risk areas in West- and Central Africa. Although loiasis is associated with significant morbidity and excess mortality, little is known about the perception of loiasis by affected communities. This study assessed the knowledge, attitudes, and practices in the rural population of Sindara, Gabon, a region characterized by high loiasis prevalence. METHODS: A community-based cross-sectional survey was conducted in Gabon between January and June 2022. During systematic door-to-door visits, randomly selected inhabitants were invited to participate in this questionnaire based survey. Venous blood was collected at midday from all participants for microscopic detection of filarial infection and clinical signs of loiasis were assessed. RESULTS: A total of 150 participants were recruited, of which 66% were infected by L. loa. While almost everyone had some knowledge about L. loa, 72% of the participants understood that L. loa is a parasitic worm. The transmission of L. loa via the deer fly was known to only 21% of participants. The most frequently mentioned clinical symptoms attributed to loiasis were itching (84%), eye worm migration (59%), and conjunctivitis-like symptoms (53%). Participants who experienced migratory loiasis had better knowledge of loiasis and considered it as more serious. Traditional and herbal medicine was reported most often as an available treatment option (72%). While the formal healthcare sector was mentioned as the preferred treatment provider, 60% of the reported infections were treated by traditional medical practitioners. CONCLUSION: Loiasis is in general well known by this community residing in a region of high L. loa transmission. Important gaps in knowledge were discovered foremost regarding the mode of transmission. The available healthcare system does not seem to provide adequate management for loiasis.

Analysis of diagnostic test outcomes in a large loiasis cohort from an endemic region: Serological tests are often false negative in hyper-microfilaremic infections.

BACKGROUND: The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region. METHODS: Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis. RESULTS: ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively. CONCLUSION: None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations.

Safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin-piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs. METHODS: For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin-piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2-10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16-27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109. FINDINGS: From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03-0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27-0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups. INTERPRETATION: In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin-piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Investigation on birth weight outcomes in schistosomiasis and praziquantel research: a correspondence.

Infection with Schistosoma sp. during pregnancy can cause low birth weight of the newborn. To allow a better differentiation between newborns with low birth weight and those with normal weight, the terms of intrauterine growth restriction (IUGR), small for gestational age (SGA) or fetal growth restriction (FGR) should be used. FGR describes the relationship between birth weight and gestational age and is defined as the incapability of a fetus to achieve expected growth with birth weight below the 10th percentile for gestational age. Additional investigations of the proportion of newborns with FGR should obtain more certainty about the effect of praziquantel and schistosomiasis on fetal growth.

Epidemiology of co-infections in pregnant women living with human immunodeficiency virus 1 in rural Gabon: a cross-sectional study.

BACKGROUND: There is no recent epidemiological data on HIV infection in Gabon, particularly in pregnant women. To close this gap, an HIV-prevalence survey was conducted among Gabonese pregnant women, followed by a cross-sectional case-control study in which the prevalence of various co-infections was compared between HIV-positive and HIV-negative pregnant women. METHODS: Between 2018 and 2019, data for the HIV-prevalence survey were collected retrospectively in 21 Gabonese antenatal care centres (ANCs). Subsequently, for the prospective co-infection study, all HIV-positive pregnant women were recruited who frequented the ANC in Lambaréné and a comparator sub-sample of HIV-negative pregnant women was recruited; these activities were performed from February 2019 to February 2020. The mean number of co-infections was ascertained and compared between HIV-positive and HIV-negative women. Additionally, the odds for being co-infected with at least one co-infection was evaluated and compared between HIV-positive and HIV-negative women. RESULTS: HIV-positivity was 3.9% (646/16,417) among pregnant women. 183 pregnant women were recruited in the co-infection study. 63% of HIV-positive and 75% of HIV-negative pregnant women had at least one co-infection. There was a trend indicating that HIV-negative women were more often co-infected with sexually transmitted infections (STIs) than HIV-positive women [mean (standard deviation, SD): 2.59 (1.04) vs 2.16 (1.35), respectively; P = 0.056]; this was not the case for vector-borne infections [mean (SD): 0.47 (0.72) vs 0.43 (0.63), respectively; P = 0.59]. CONCLUSIONS: Counterintuitively, the crude odds for concomitant STIs was lower in HIV-positive than in HIV-negative women. The change of magnitude from the crude to adjusted OR is indicative for a differential sexual risk factor profile among HIV-positive and HIV-negative women in this population. This might potentially be explained by the availability of sexual health care counselling for HIV-positive women within the framework of the national HIV control programme, while no such similar overall service exists for HIV-negative women. This highlights the importance of easy access to sexual healthcare education programmes for all pregnant women irrespective of HIV status.

Prevalence and impact of SARS-CoV-2 infection on maternal and infant health in African populations: protocol of a multicentre prospective cohort study (MA-CoV project).

INTRODUCTION: Pregnant women are currently considered a vulnerable population to SARS-CoV-2 infection, with increased risk of severe COVID-19, preterm birth and maternal mortality. There is, however, a paucity of data on the burden of maternal SARS-CoV-2 infection in sub-Saharan countries. The objective of this study is to determine the prevalence and health effects of maternal SARS-CoV-2 infection in selected sites from Gabon and Mozambique. METHODS AND ANALYSIS: MA-CoV (MAternal CoVid) is an observational, multicentre prospective cohort study where 1000 pregnant women (500 per country) will be enrolled at the antenatal clinic visits. Participants will undergo monthly follow-up at each antenatal care visit, delivery and postpartum visit. The primary study outcome is the prevalence of SARS-CoV-2 infection during pregnancy. The clinical presentation of COVID-19 in pregnancy will also be characterised, and incidence of infection during pregnancy will be evaluated, as well as the risk factors of maternal and neonatal morbidity and mortality associated with SARS-CoV-2 infection and the risk of mother to child transmission of SARS-CoV-2. SARS-CoV-2 infection screening will be performed through PCR diagnosis. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Comité National d'Éthique pour la Recherche au Gabon, Comité Nacional de Bioética para Saúde de Moçambique and the Ethics Committee of the Hospital Clinic of Barcelona (Spain). Project results will be presented to all stakeholders and published in open access journals. TRIAL REGISTRATION NUMBER: NCT05303168.

Efficacy, safety, and tolerability of albendazole and ivermectin based regimens for the treatment of microfilaraemic loiasis in adult patients in Gabon: A randomized controlled assessor blinded clinical trial.

BACKGROUND: There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon. METHODS: Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168. RESULTS: In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80-90% reduction of microfilaraemia was observed in the active treatment groups. CONCLUSION: The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe. TRIAL REGISTRATION: Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027.

[Malaria and its importance in travel medicine]. / Malaria und ihre Bedeutung in der Reisemedizin.

Malaria remains one of the most important infectious diseases worldwide. The annual number of cases is currently estimated at around 240 million globally, of which more than 500,000 cases are fatal. The majority of malaria cases in Europe are imported from the African continent. Plasmodium falciparum, the causative agent of malaria tropica, causes 75-90 % of all infections imported to Germany. Artemisinin-based combination therapies are the standard treatment for uncomplicated malaria worldwide. In addition to uncomplicated malaria infections, Plasmodium falciparum can cause severe malaria, characterized by vital organ dysfunction and hyperparasitaemia. The treatment of choice for severe malaria is parenteral artesunate. For all patients presenting with febrile illness after a stay in a malaria-endemic area malaria must be ruled out immediately. Microscopy of the thick drop remains the gold standard for diagnosis in clinical routine.