Background:Adjunctive corticosteroid therapy appears to be beneficial for adults with severe community-acquired pneumonia (CAP), but data on Mycoplasma pneumoniae CAP are limited. This study aimed to evaluate if adjunctive betamethasone reduced time to resolution of hypoxaemia in adults hospitalised with M. pneumoniae CAP. Methods:An open-label, multicentre, randomised, controlled trial was conducted at eight Swedish hospitals. Adults admitted with M. pneumoniae CAP and hypoxaemia (SpO2 <93% and respiratory rate >20 breaths/min) were eligible. Exclusion criteria included asthma and diabetes mellitus. Participants were randomised (1:1) to either standard care without corticosteroids or adjunctive oral betamethasone (3 mg daily on days 1-2, and 2 mg daily on days 3-5). Antibiotic treatment was standardised to 200 mg doxycycline once daily for 10 days. The primary outcome was time to resolution of hypoxaemia in an intention-to-treat analysis. Safety was assessed in participants receiving at least one betamethasone dose. The study was registered with the EU Clinical Trials Register (EudraCT 2016-002585-32) and is completed. Findings:Between March 1, 2018, and November 14, 2024, 70 participants were enrolled: 36 in the betamethasone group and 34 in the control group. The median age was 42 years (IQR 28-49) including 40 (57%) male and 30 (43%) female participants. All participants achieved resolution of hypoxaemia except two who withdrew consent. Time to resolution of hypoxaemia was shorter in the betamethasone group (HR 1.82 [95% CI 1.10-3.02], p = 0.020) compared to the standard of care group, with an estimated median of 2.3 (95% CI 1.8-2.7) and 3.6 (95% CI 1.9-5.3) days, respectively. Adverse events were similar between study groups. Severe adverse events were rare, and none were attributed to betamethasone treatment. Interpretation:Adjunctive betamethasone was well tolerated and significantly shortened the duration of hypoxaemia in adults hospitalised with M. pneumoniae CAP in this open-label trial. Funding:The Swedish Society of Medicine.

Background:This study aimed to describe the incidence rate, patient characteristics, treatments, and outcomes of adults hospitalized with Mycoplasma pneumoniae pneumonia. Methods:This retrospective cohort study included adults diagnosed with M pneumoniae pneumonia and admitted to emergency care hospitals in Stockholm County, Sweden, from 2013 to 2017. Patients were identified through positive M pneumoniae polymerase chain reaction and ICD-10 code J15.7 (M pneumoniae pneumonia). Medical records were reviewed manually, and population data were extracted from statistical databases. Incidence rates were calculated, and treatment outcomes were analyzed using regression models. Results:A total of 747 adults with a median age of 42 (interquartile range [IQR], 33-55) years, of whom 55% (385/747) were male, were hospitalized with M pneumoniae pneumonia. The incidence rate was 8.5 cases per 100 000 person-years, peaking at 14.1 in 2016. Cough (95%) and fever (92%) were the most common symptoms, and 71% were hypoxemic at admission. Patients with severe disease had longer symptom duration at admission. In-hospital mortality was 0.4%, and 6% required intensive care unit admission. Median length of stay (4 [IQR, 2-6] days) was longer in patients treated with macrolides (+1.0 [IQR, 0.9-1.2] days; P < .001) and fluoroquinolones (+0.8 [IQR, 0.1-1.4] days; P = .03) compared to those treated with tetracyclines. The median fever duration was significantly longer (+0.3 [IQR, 0.1-0.6] days; P = .02) in patients treated with fluoroquinolones compared to those treated with tetracyclines. Conclusions:The study highlights the importance of timely and accurate treatment of M pneumoniae pneumonia. Tetracycline treatment was associated with better outcomes, suggesting they may be an effective first-line treatment option.

Recurrent Clostridioides difficile infection is most effectively treated with faecal microbiota transplantation. Swedish and European guidelines suggest faecal microbiota transplantation after a first or second recurrence, respectively. The aims of this study were to evaluate risk factors for further relapses at the first and second recurrence, related to treatment recommendations. Patients aged ≥ 18 years with two positive tests for C. difficile within eight weeks and treated at the study hospitals during 2014–2022 were eligible for inclusion. Retrospectively collected data included age, sex, treatment, and clinical characteristics for each episode. Risk factors for further recurrences at the first and second recurrence were identified using multivariable logistic regression analysis. The median age in the total cohort (n = 231) was 76 (IQR 67–84) years, 52

Background: Corticosteroids appears to be beneficial for severe Mycoplasma pneumoniae pneumonia in children, but data in adults are limited. This study investigated effects of adjunctive corticosteroids in hypoxemic adults with M. pneumoniae pneumonia. Methods: Adults admitted 2013-2017 with verified M. pneumoniae pneumonia and hypoxemia (SpO(2) < 93% or oxygen treatment) were included in a cohort. Treatment was defined as receipt of at least 1 glucocorticoid dose. Primary outcome was time to regression of hypoxemia, analyzed with a multivariable Cox regression. Secondary outcomes included fever duration, length of stay, and complications. Results: Corticosteroids were given to 31% (122/388) during hypoxemia. Median age was 44 (interquartile range [IQR] 34-57) years. Median time to start of corticosteroid treatment was 1.9 (IQR 0.6-3.6) days from admission. Median cumulative dose was equivalent to 15 (IQR 10-19) mg betamethasone. Treatment duration was 5 (IQR 3-6) days. Patients treated with corticosteroids had more severe respiratory disease, longer symptom duration, and were more often treated with fluoroquinolones. Time to regression of hypoxemia (hazard ratio [HR] 0.92 [95% confidence interval {CI}: .72-1.19], P = .53) and length of stay (HR 0.91 [95% CI: .71-1.16], P = .44) were not significantly different between corticosteroid treated and controls. Corticosteroid treatment was associated to shorter fever duration (HR 1.44 [95% CI: 1.00-2.06], P = .046). Complications did not differ significantly between treatment groups. Conclusions: Adjunctive corticosteroids were not associated with reduced time to regression of hypoxemia in adults with M. pneumoniae pneumonia. However, duration of fever was shorter and no increase in complications was seen.

BACKGROUND:Endocarditis occurs in approximately 10%-15% of patients with Staphylococcus aureus bacteremia (SAB). Short time to positivity (TTP) in blood culture flasks has been linked to endocarditis in smaller studies. This study evaluated the association between TTP and endocarditis in SAB in a large cohort. METHODS:Adult patients with ≥1 S. aureus positive blood culture treated at a tertiary-level, 500-bed hospital in Stockholm, Sweden between 2011-2021 were retrospectively identified. The primary outcome was the presence of infective endocarditis. RESULTS:A total of 1703 episodes of SAB (23/1703 methicillin-resistant) in 1610 patients were included. Median age was 75 (interquartile range [IQR], 63-84) years and median Charlson comorbidity index score was 2 (IQR, 1-3). Echocardiography was performed in 1102/1703 (65%). Thirty-day mortality was 406/1703 (24%) and endocarditis was found in 154/1703 (9%). Median TTP was shorter in patients with endocarditis (9 [IQR, 7-12] hours) compared to patients without endocarditis (13 [interquartile range, 10-18] hours; P < .001). The risk of endocarditis decreased with 11% per hour (odds ratio [OR], 0.89 [95% confidence interval {CI}, .54-.92]; P < .001) in a univariate analysis using TTP as a continuous variable. In multivariate analysis, TTP <13 hours (the median) was independently associated with endocarditis (OR, 3.59 [95% CI, 2.35-5.3]; P < .001). The negative predictive value of TTP >13 hours for endocarditis was 96% (95% CI, 95%-97%). CONCLUSIONS:Short TTP was associated with endocarditis. The negative predictive value of >95% suggests that TTP >13 hours can be used to risk-stratify patients with SAB.

In this Review, we analysed the prevalence of viraemia during infection with SARS-CoV-2 and other relevant respiratory viruses, including other human coronaviruses such as MERS-CoV and SARS-CoV, adenovirus, human metapneumovirus, human rhinovirus/enterovirus, influenza A and B virus, parainfluenza virus, and respiratory syncytial virus. First, a preliminary systematic search was conducted to identify articles published before May 23, 2024 that reported on viraemia during infection with respiratory viruses. The articles were then analysed for relevant terms to identify the prevalence of viraemia, its association with the disease severity and long-term consequences, and host responses. A total of 202 articles were included in the final study. The pooled prevalence of viraemia was 34% for SARS-CoV-2 and between 6% and 65% for other viruses. Association of viraemia with disease severity was extensively reported for SARS-CoV-2 and also for SARS-CoV, MERS-CoV, adenoviruses, rhinoviruses, respiratory syncytial virus, and influenza A(H1N1)pdm09 (albeit with low evidence). SARS-CoV-2 viraemia was linked to memory problems and worsened quality of life. Viraemia was associated with signatures denoting dysregulated host responses. In conclusion, the high prevalence of viraemia and its association with disease severity suggests that viraemia could be a relevant pathophysiological event with important translational implications in respiratory viral infections.

Background Diarrhoea remains a major cause of childhood morbidity and mortality in low-income countries (LICs). The frequency of diarrhoeal episodes may vary by season, yet few prospective cohort studies have examined seasonal variation among various diarrhoeal pathogens using multiplex qPCR to analyse bacterial, viral and parasitic pathogens. Methods We combined our recent qPCR data of diarrhoeal pathogens (nine bacterial, five viral and four parasitic) among Guinea-Bissauan children under five years old with individual background data, dividing by season. The associations of season (dry winter and rainy summer) and the various pathogens were explored among infants (0–11 months) and young children (12–59 months) and those with and without diarrhoea. Results Many bacterial pathogens, especially EAEC, ETEC and Campylobacter , and parasitic Cryptosporidium , prevailed in the rainy season, whereas many viruses, particularly the adenovirus, astrovirus and rotavirus proved common in the dry season. Noroviruses were found constantly throughout the year. Seasonal variation was observed in both age groups. Conclusion In childhood diarrhoea in a West African LIC, seasonal variation appears to favour EAEC, ETEC, and Cryptosporidium in the rainy and viral pathogens in the dry season.

BACKGROUND:Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking.AIMS:To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics.METHOD:Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed.RESULTS:Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8).CONCLUSION:Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo.TRIAL REGISTRATION:EudraCT 2017-002418-30.

Abstract Background Studies on the antiviral effects of remdesivir have shown conflicting results. SARS-CoV-2 viraemia could identify patients in whom antiviral treatment may be particularly beneficial. Objectives To investigate antiviral effects and clinical outcomes of remdesivir treatment in viraemic patients. Methods Viraemic patients hospitalized for COVID-19 with ratio of arterial oxygen partial pressure to fractional inspired oxygen of ≤300, symptom duration ≤10 days, and estimated glomerular filtration rate ≥30 mL/min were included in a cohort. The rate of serum viral clearance and serum viral load decline, 60 day mortality and in-hospital outcomes were estimated. A subgroup analysis including patients with symptom duration ≤7 days was performed. Results A total of 318 viraemic patients were included. Thirty-three percent (105/318) received remdesivir. The rate of serum viral clearance [subhazard risk ratio (SHR) 1.4 (95% CI 0.9–2.0), P = 0.11] and serum viral load decline (P = 0.11) were not significantly different between remdesivir-treated patients and controls. However, the rate of serum viral clearance was non-significantly higher [SHR 1.6 (95% CI 1.0–2.7), P = 0.051] and the viral load decline was faster (P = 0.03) in remdesivir-treated patients with symptom duration ≤7 days at admission. The 60 day mortality [HR 1.0 (95% CI 0.6–1.8), P = 0.97] and adverse in-hospital outcomes [OR 1.4 (95% CI 0.8–2.4), P = 0.31] were not significantly different between remdesivir-treated patients and controls. Conclusions Remdesivir treatment did not significantly change the duration of SARS-CoV-2 viraemia, decline of serum viral load, 60 day mortality or in-hospital adverse outcomes in patients with ≤10 days of symptoms at admission. Remdesivir appeared to reduce the duration of viraemia in a subgroup of patients with ≤7 days of symptoms at admission.

To the Editor, Atovaquone (250 mg)/proguanil (100 mg) (AP, Malarone®, GlaxoSmithKline, UK) is the most frequently prescribed chemoprophylaxis against malaria by travellers.1 Atovaquone, the key component, mainly acts against Plasmodium falciparum asexual blood stages, having also a marked malaria transmission blocking effect. Proguanil synergizes with atovaquone, potentially protecting each other from the development of resistance. Oral bioavailability of atovaquone is low (~25%), but improves following a high-fat diet. It appears to clearance slowly with extensive enterohepatic recycling and an elimination half-life of 2–4 days.2 Phase I metabolism is negligible2,3 and when taken repeatedly as chemoprophylaxis with proguanil, over 90% of the absorbed atovaquone is recovered in stool unchanged and a small fraction (<0.6%) in the urine.4 The underlying elimination mechanisms are, however, poorly understood. Serious adverse events associated with AP are rare but mild ones are relatively frequent, especially after repeated administration in prophylactic doses4 potentially affecting the compliance. Understanding the mechanisms of atovaquone disposition is key to better predict and prevent potential drug–drug interactions leading to dose-dependent AP side effects.

Fluoroquinolones and macrolides may, due to a potential drug‐drug interaction, increase the concentration of any concomitantly administered direct oral anticoagulant (DOAC) and thereby increase the risk of severe bleeding. However, clinical evidence for such an effect is scarce. The present study aimed to evaluate the association between the use of fluoroquinolones or macrolides and bleeding events in patients with concomitant DOAC use. This was a nationwide cohort study including 19 288 users of DOACs in 2008‐2018 using information from Swedish national health registers. We compared the incidence of bleeding events associated with use of fluoroquinolones or macrolides using doxycycline as a negative control. Cox regression was used to calculate crude and adjusted hazard ratios (aHRs) in time windows of various length of follow‐up after the start of antibiotic use. The incidence rates for fluoroquinolones and macrolides ranged from 12 to 24 and from 12 to 53 bleeding events per 100 000 patients in the investigated time windows. The aHRs (95% confidence interval) for use of fluoroquinolones and macrolides were 1.29 (0.69‐2.44) and 2.60 (0.74‐9.08) at the concomitant window, 1.31 (0.84‐2.03) and 1.79 (0.75‐4.29) at 30 days, and 1.34 (0.99‐1.82) and 1.28 (0.62‐2.65) at 150 days, respectively. With regard to fluoroquinolones, the present study suggests that the risk of bleeding when combined with DOACs, if any, is small. Codispensation of macrolides in patients on DOACs was not associated with an increased risk of bleeding. However, due to the small number of macrolide users, the results must be interpreted with caution.

BACKGROUND:Plasmodium falciparum strains that are resistant to standard-dose chloroquine can be treated by higher chloroquine concentrations maintained for a longer time in vivo.OBJECTIVES:To determine the relative importance of chloroquine concentrations versus exposure time for elimination of chloroquine-susceptible and -resistant P. falciparum in vitro.METHODS:Chloroquine-susceptible (3D7) and -resistant (FCR3) strains were exposed in vitro to 1, 2, 4, 8, 16 or 32 times their respective 90% inhibitory chloroquine concentrations for 3, 5, 7 or 14 days and then followed until recrudescence, or not, by 42 days after the end of exposure.RESULTS:Exposure to chloroquine appeared to eliminate susceptible and resistant parasites, leaving small pyknotic apparently dead parasites. Chloroquine-susceptible and -resistant parasites recrudesced after 3 and 5 days of chloroquine exposure. Recrudescence occurred in one out of four 7 day exposure series but not after 14 days exposure. The median time to recrudescence was 13 to 28 days with a range of 8 to 41 days after the end of exposure. Time to recrudescence after the end of exposure increased with duration of exposure for susceptible and resistant strains (P < 0.001). Time to recrudescence did not correlate with concentrations greater than 1× IC90.CONCLUSIONS:Chloroquine-susceptible and -resistant P. falciparum probably become dormant. Elimination of dormant parasites is primarily dependent upon the duration of chloroquine exposure. Exposure to effective drug concentrations for 7 days eliminates most parasites in vitro. The results support in vivo data indicating that elimination of chloroquine-resistant P. falciparum correlates with Day 7 chloroquine concentrations.

SARS-CoV-2 viremia at admission is associated with high risk for mortality. However, longitudinal data on viremia duration are limited. Viremic patients hospitalized for COVID-19 were included in a cohort. Time to serum viral clearance and the effect of viremia duration on the odds of mortality were calculated. One hundred and twenty-one viremic patients were included. Median age was 62 (IQR 52-71) years and 68% were males. The total in-hospital mortality of the cohort was 33%. Median time from admission to serum viral clearance was 7 (95% CI 6-8) days. Duration of viremia showed a relative risk ratio of 1.40 (95% CI 1.02-1.92) for the odds of mortality in an adjusted multinomial logistic regression. Serum viral clearance coincided with defervescence and decreasing C-reactive protein. Median time to serum viral clearance was 7 days after admission. The odds of mortality increased with 40% for each additional day of viremia.

Abstract Background Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viremia and nasopharyngeal viral load have been suggested to be predictors of unfavorable outcome in coronavirus disease 2019 (COVID-19). This study aimed to investigate whether nasopharyngeal viral load is correlated with viremia and unfavorable outcome. Methods The presence of SARS-CoV-2 RNA was determined in paired nasopharyngeal and serum samples collected at admission from patients hospitalized for COVID-19. Standardized cycle threshold values (CT values) were used as an indicator of viral load. An adjusted logistic regression was used to estimate the risk of viremia at different nasopharyngeal CT values. A Cox regression was used to estimate the risk of 60-day mortality. Results A total of 688 patients were included. Viremia at admission was detected in 63% (146/230), 46% (105/226), and 31% (73/232) of patients with low, intermediate, and high nasopharyngeal CT values. The adjusted odds ratios of being viremic were 4.4 (95% CI, 2.9–6.8) and 2.0 (95% CI, 1.4–3.0) for patients with low and intermediate CT values, compared with high CT values. The 60-day mortality rate was 37% (84/230), 15% (36/226), and 10% (23/232) for patients with low, intermediate, and high nasopharyngeal CT values at admission, respectively. Adjusted hazard ratios were 2.6 (95% CI, 1.6–4.2) and 1.4 (95% CI, 0.8–2.4) for patients with low and intermediate CT values compared with high CT values. Conclusions There was a dose-dependent correlation between nasopharyngeal CT values and viremia at admission for COVID-19. Moreover, there was an increased risk of 60-day mortality for patients with low, compared with high, nasopharyngeal CT values.

Background Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages. Methods Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0–11 and 12–59 months. Results Of the 429 children– 228 with and 201 without diarrhoea– 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E . coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E . coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E . coli (EIEC)/ Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/ Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/ Shigella , Giardia duodenalis and Dientamoeba fragilis among the older children. Conclusions Stool pathogens proved common among all the children regardless of them having diarrhoea or not.

Introduction Although there are many studies on the use of convalescent plasma (CP) for treatment of COVID-19, it is not clear (1) which groups of patients may benefit, (2) what dose of plasma to give, or (3) which antibody levels the plasma should contain. Previous phase I/II studies and literature review suggest that CP should only be given to patients with viraemia, that a daily infusion should be given until the patient becomes virus free and that the neutralising antibody titre should preferably be >1:640Methods and analysis An open randomised controlled trial enrolling patients with COVID-19, who must be SARS-CoV-2 positive in both airway and blood samples and admitted to a study hospital. Block randomisation 2:1 is to either 200 mL CP (preferably titre ≥1/640) daily for up to 10 days (until virus negative in blood) plus standard care or standard care only (control arm). The primary endpoint is mortality by day 28 after study inclusion. Secondary endpoints include mortality by day 60 and doses of plasma needed to clear viraemia. Assuming a reduced mortality of approximately 30% by the CP therapy and 85%–88% survival in the control arm, approximately 600 participants will be enrolled to the CP therapy arm and 300 participants to the control arm.Ethics and dissemination Ethical approval has been granted by the Swedish Ethical Review Authority (reference: 2020-06277). Results from this trial will be compiled in a clinical study report, disseminated via journal articles and communicated to stakeholders.Trial registration number NCT04649879.

BACKGROUNDSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 RNA in serum at admission correlated with clinical outcome in COVID-19.METHODSCOVID-19 patients admitted to the Infectious Diseases department of a tertiary level Swedish hospital, and sampled for SARS-CoV-2 RNA in serum at admission, April 10 to June 30 2020 were included in a cohort. Primary outcomes were day 28 all-cause mortality and progress to critical disease.RESULTSThe cohort (N=167) consisted of 106 SARS-CoV-2 RNA serum negative and 61 positive patients. Median sampling time for initial SARS-CoV-2 in serum was 1 (IQR 1-2) day after admission corresponding to day 10 (IQR 8-12) after symptom onset. Median ages were 53 (IQR 44-67) and 63 (IQR 52-74) years for the PCR-negative and positive patients, respectively. In the serum PCR negative and positive groups 3/106 and 15/61 patients died, respectively.The hazard ratios for critical disease and all-cause mortality were 7.2 (95% CI 3.0-17) and 8.6 (95% CI 2.4-30), respectively for patients that were serum PCR positive compared to serum PCR negative.Conclusion: SARS-CoV-2 RNA in serum at hospital admission indicates a high-risk of progression to critical disease and death.

ObjectiveTo evaluate the effectiveness and tolerability of secnidazole combined with high-dose mebendazole for treatment of 5-nitroimidazole-resistant giardiasis.MethodAdults with microscopically verified Giardia intestinalis monoinfection attending a secondary level hospital in Matanzas City, Cuba were prospectively included in a cohort. A recently introduced treatment ladder consisting of metronidazole as first-line treatment, followed by secnidazole, tinidazole, secnidazole plus mebendazole and quinacrine as second-to fifth-line treatments, respectively, was used. Adverse events and treatment success were determined by questioning and microscopy on concentrated stool samples, respectively on days 3, 5 and 7 after the end of treatment. If G. intestinalis was detected on day 3, 5 or 7, then the infection was classified as refractory and no further microscopy was performed.ResultsA total of 456 individuals were included. Metronidazole, 500 mg three times daily for 5 days, cured 248/456 (54%) patients. A single 2-g secnidazole dose as second-line treatment cured 50/208 (24%) patients. A single 2-g tinidazole dose as third-line treatment cured 43/158 (27%) patients. Three rounds of 5-nitroimidazole therapy therefore cured 341/456 (75%) patients. Secnidazole plus mebendazole (200 mg every 8 hours for 3 days) cured 100/115 (87%) of nitroimidazole refractory infections. Quinacrine cured the remaining 15 patients. All treatments were well tolerated.Conclusions5-Nitroimidazole refractory giardiasis was common, indicating that an alternative first-line treatment may be needed. Retreatment of metronidazole refractory giardiasis with an alternative 5-nitroimidazole was suboptimal, indicating cross-resistance. Mebendazole plus secnidazole were well tolerated and effective for the treatment of 5-nitroimidazole refractory G. intestinalis infection in this setting.

The BCG vaccine protects non-specifically against other diseases than tuberculosis. Three randomised controlled trials of early BCG in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality. Little is known about the underlying mechanisms. In Guinea-Bissau, prevalent infectious diseases display distinct seasonality. Revisiting the three trials (>6500 infants) comparing early BCG versus no early BCG in low weight infants on all-cause neonatal mortality over 12 consecutive years, we explored the seasonal variation in BCG’s effect on mortality. In a subgroup of participants, adaptive and innate cytokine responses were measured 4 weeks after randomisation. Consistently over the course of the three trials and 12 years, the effect of BCG on all-cause neonatal mortality was particularly beneficial when administered in November to January, coincident with peaking malaria infections. During these months, BCG was also associated with stronger proinflammatory responses to heterologous challenge. Recent studies have suggested a protective effect of BCG against malaria. BCG may also ameliorate immune-compromising fatal effects of placental malaria in the newborn.