Evaluation and validation of a PrintrLab-based LAMP assay to identify Trypanosoma cruzi in newborns in Bolivia: a proof-of-concept study.

BACKGROUND: Vertical transmission of Trypanosoma cruzi represents approximately 20% of new Chagas disease cases. Early detection and treatment for women of childbearing age and newborns is a public health priority, but the lack of a simple and reliable diagnostic test remains a major barrier. We aimed to evaluate the performance of a point-of-care loop-mediated isothermal amplification (LAMP) assay for the detection of T cruzi. METHODS: In this proof-of-concept study, we coupled a low-cost 3D printer repurposed for sample preparation and amplification (PrintrLab) to the Eiken T cruzi-LAMP prototype to detect vertically transmitted T cruzi, which we compared with standardised PCR and with the gold-standard algorithm (microscopy at birth and 2 months and serological study several months later). We screened pregnant women from two hospitals in the Bolivian Gran Chaco province, and those who were seropositive for T cruzi were offered the opportunity for their newborns to be enrolled in the study. Newborns were tested by microscopy, LAMP, and PCR at birth and 2 months, and by serology at 8 months. FINDINGS: Between April 23 and Nov 17, 2018, 986 mothers were screened, among whom 276 were seropositive for T cruzi (28·0% prevalence, 95% CI 25·6-31·2). In total, 224 infants born to 221 seropositive mothers completed 8 months of follow-up. Congenital transmission was detected in nine of the 224 newborns (4·0% prevalence, 1·9-7·5) by direct microscopy observation, and 14 more cases were diagnosed serologically (6·3%, 3·6-10·3), accounting for an overall vertical transmission rate of 10·3% (6·6-15·0; 23 of 224). All microscopy-positive newborns were positive by PrintrLab-LAMP and by PCR, while these techniques respectively detected four and five extra positive cases among the remaining 215 microscopy-negative newborns. INTERPRETATION: The PrintrLab-LAMP yielded a higher sensitivity than microscopy-based analysis. Considering the simpler use and expected lower cost of LAMP compared with PCR, our findings encourage its evaluation in a larger study over a wider geographical area. FUNDING: Inter-American Development Bank.

Screening and routine diagnosis of mental disorders among migrants in primary care: A cross-sectional study.

Background: Migrants in host countries are at risk for the development of mental health conditions. The two aims of the study were to describe routine diagnoses of mental disorders among migrant patients at primary healthcare level and the associated risk factors, and to test the utility of an innovative migrant mental health assessment by evaluating whether the health professionals followed the recommendations proposed by the clinical decision support system (CDSS) tool. Methods: A cross-sectional study was carried out in eight primary care centres (PCCs) in four non-randomly selected health regions of Catalonia, Spain from March to December 2018. Routine health data and mental health diagnoses based on the International Classification of Diseases (10th edition), including mental, behavioural and neuro developmental disorders (F01-F99), symptoms and signs involving emotional state (R45), and sleep disorders (G47), were extracted from the electronic health records. The proportion of mental health conditions was estimated and logistic regression models were used to assess any possible association with mental health disorders. The utility of the mental health assessment was assessed with the proportion of questionnaires performed by health professionals for migrants fulfilling the mental health screening criterion (country of origin with an active conflict in 2017) and the diagnoses given to the screened patients. Results: Of 14,130 migrants that visited any of the PCCs during the study period, 7,358 (52.1 %) were women with a median age of 38.0 years-old. There were 520/14,130 (3.7 %) migrant patients diagnosed with a mental disorder, being more frequent among women (342/7,358; 4.7 %, p-value < 0.001), migrants from Latin-America (177/3,483; 5.1 %, p < 0.001) and those who recently arrived in Spain (170/3,672; 4.6 %, p < 0.001). A lower proportion of mental disorders were reported in migrants coming from conflicted countries in 2017 (116/3,669, 3.2 %, p = 0.053).Out of the 547 mental health diagnoses reported in 520 patients, 69/14,130 (0.5 %) were mood disorders, 346/14,130 (2.5 %) anxiety disorders and 127/14,130 (0.9 %) sleeping disorders. Mood disorders were more common in migrants from Eastern Europe (25/2,971; 0.8 %, p < 0.001) and anxiety disorders in migrants from Latin-America (126/3,483; 3.6 %, p < 0.001), while both type of disorders were more often reported in women (p < 0.001).In the adjusted model, women (aOR: 1.5, [95 % CI 1.2-1.8, p < 0.001]), migrants with more than one visit to the health center during the study period (aOR: 4.4, [95 %CI 2.8-6.8, p < 0.001]) and who presented an infectious disease (aOR: 2.1, [95 %CI 1.5-3.1, p < 0.001]) had higher odds of having a mental disorder.Lastly, out of the 1,840 migrants coming from a conflicted country in 2017 who were attended in centres where the CDSS tool was implemented, 29 (1.6 %) had a mental health assessment performed and the tool correctly identified one individual. Conclusions: Mental health is a condition that may be overlooked in migrants at primary healthcare. Interventions at this level of care must be reinforced and adapted to the needs and circumstances of migrants to ensure equity in health services.

Five-year serological and clinical evolution of chronic Chagas disease patients in Cochabamba, Bolivia.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment-benznidazole and nifurtimox-but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year. CONCLUSIONS/SIGNIFICANCE: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols.

Alternative approaches for creating a wealth index: the case of Mozambique.

INTRODUCTION: The wealth index is widely used as a proxy for a household's socioeconomic position (SEP) and living standard. This work constructs a wealth index for the Mopeia district in Mozambique using data collected in year 2021 under the BOHEMIA (Broad One Health Endectocide-based Malaria Intervention in Africa) project. METHODS: We evaluate the performance of three alternative approaches against the Demographic and Health Survey (DHS) method based wealth index: feature selection principal components analysis (PCA), sparse PCA and robust PCA. The internal coherence between four wealth indices is investigated through statistical testing. Validation and an evaluation of the stability of the wealth index are performed with additional household income data from the BOHEMIA Health Economics Survey and the 2018 Malaria Indicator Survey data in Mozambique. RESULTS: The Spearman's rank correlation between wealth index ventiles from four methods is over 0.98, indicating a high consistency in results across methods. Wealth rankings and households' income show a strong concordance with the area under the curve value of ~0.7 in the receiver operating characteristic analysis. The agreement between the alternative wealth indices and the DHS wealth index demonstrates the stability in rankings from the alternative methods. CONCLUSIONS: This study creates a wealth index for Mopeia, Mozambique, and shows that DHS method based wealth index is an appropriate proxy for the SEP in low-income regions. However, this research recommends feature selection PCA over the DHS method since it uses fewer asset indicators and constructs a high-quality wealth index.

Burden and risk factors of snakebite in Mopeia, Mozambique: Leveraging larger malaria trials to generate data of this neglected tropical disease.

BACKGROUND: Snakebite is a neglected disease that disproportionally affects the rural poor. There is a dearth of evidence regarding incidence and risk factors in snakebite-endemic countries. Without this basic data, it will be impossible to achieve the target of a 50% reduction of snakebite morbidity and mortality by 2030 as set by the World Health Organization. METHODS: This was a descriptive analysis nested in a 2021 community-based demographic survey of over 70,000 individuals conducted in Mopeia, Mozambique, in preparation for a cluster randomized trial to test an intervention for malaria. We describe the incidence rate, demographics, socioeconomic indicators and outcomes of snakebite in this population. FINDINGS: We found the incidence of self-reported snakebite in Mopeia to be 393 bites per 100,000 person-years at risk, with 2% of households affected in the preceding 12 months. Whilst no fatalities were recorded, over 3,000 days of work or school days were lost with an individual household economic impact higher than that of uncomplicated malaria. 1 in 6 of those affected did not fully recover at the time of the study. We found significant relationships between age older than 15, use of firewood for household fuel, and animal possession with snakebite. CONCLUSIONS: This study exposes higher than expected incidence and burden of snakebite in rural Mozambique. Whilst snakebite elimination in Mozambique seems unattainable today, it remains a preventable disease with manageable sequelae. We have shown that snakebite research is particularly easy to nest in larger studies, making this a practical and cost-effective way of estimating its incidence.

Burden and risk factors of snakebite in Mopeia, Mozambique: Leveraging larger malaria trials to generate data of this neglected tropical disease

Background: Snakebite is a neglected disease that disproportionally affects the rural poor. There is a dearth of evidence regarding incidence and risk factors in snakebite-endemic countries. Without this basic data, it will be impossible to achieve the target of a 50% reduction of snakebite morbidity and mortality by 2030 as set by the World Health Organization. Methods: This was a descriptive analysis nested in a 2021 community-based demographic survey of over 70,000 individuals conducted in Mopeia, Mozambique, in preparation for a cluster randomized trial to test an intervention for malaria. We describe the incidence rate, demographics, socioeconomic indicators and outcomes of snakebite in this population. Findings: We found the incidence of self-reported snakebite in Mopeia to be 393 bites per 100,000 person-years at risk, with 2% of households affected in the preceding 12 months. Whilst no fatalities were recorded, over 3,000 days of work or school days were lost with an individual household economic impact higher than that of uncomplicated malaria. 1 in 6 of those affected did not fully recover at the time of the study. We found significant relationships between age older than 15, use of firewood for household fuel, and animal possession with snakebite. Conclusions: This study exposes higher than expected incidence and burden of snakebite in rural Mozambique. Whilst snakebite elimination in Mozambique seems unattainable today, it remains a preventable disease with manageable sequelae. We have shown that snakebite research is particularly easy to nest in larger studies, making this a practical and cost-effective way of estimating its incidence.

Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement.

BACKGROUND: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries. METHODS: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram. RESULTS: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram. CONCLUSIONS: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators.

BACKGROUND: Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. METHODS: The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. RESULTS: 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. CONCLUSIONS: The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial. Trial registration NCT04966702.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators

Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. Methods: The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. Results: 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. Conclusions: The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial. Trial registration NCT04966702.

BOHEMIA: Broad One Health Endectocide-based Malaria Intervention in Africa-a phase III cluster-randomized, open-label, clinical trial to study the safety and efficacy of ivermectin mass drug administration to reduce malaria transmission in two African settings.

BACKGROUND: Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. METHODS: A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs DISCUSSION: The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission TRIAL REGISTRATION: ClinicalTrials.gov NCT04966702 . Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303.

Burden, clinical presentation and risk factors of advanced HIV disease in pregnant Mozambican women.

BACKGROUND: Information on the frequency and clinical features of advanced HIV disease (AHD) in pregnancy and its effects on maternal and perinatal outcomes is limited. The objective of this study was to describe the prevalence and clinical presentation of AHD in pregnancy, and to assess the impact of AHD in maternal and perinatal outcomes in Mozambican pregnant women. METHODS: This is a prospective and retrospective cohort study including HIV-infected pregnant women who attended the antenatal care (ANC) clinic at the Manhiça District Hospital between 2015 and 2020. Women were followed up for 36 months. Levels of CD4 + cell count were determined to assess AHD immune-suppressive changes. Risk factors for AHD were analyzed and the immune-suppressive changes over time and the effect of AHD on pregnancy outcomes were assessed. RESULTS: A total of 2458 HIV-infected pregnant women were enrolled. The prevalence of AHD at first ANC visit was 14.2% (349/2458). Among women with AHD at enrolment, 76.2% (260/341) were on antiretroviral therapy (ART). The proportion of women with AHD increased with age reaching 20.5% in those older than 35 years of age (p < 0.001). Tuberculosis was the only opportunistic infection diagnosed in women with AHD [4.9% (17/349)]. There was a trend for increased CD4 + cell count in women without AHD during the follow up period; however, in women with AHD the CD4 + cell count remained below 200 cells/mm3 (p < 0.001). Forty-two out of 2458 (1.7%) of the women were severely immunosuppressed (CD4 + cell count < 50 cells/mm3). No significant differences were detected between women with and without AHD in the frequency of maternal mortality, preterm birth, low birth weight and neonatal HIV infection. CONCLUSIONS: After more than two decades of roll out of ART in Mozambique, over 14% and nearly 2% of HIV-infected pregnant women present at first ANC clinic visit with AHD and severe immunosuppression, respectively. Prompt HIV diagnosis in women of childbearing age, effective linkage to HIV care with an optimal ART regimen and close monitoring after ART initiation may contribute to reduce this burden and improve maternal and child survival.

Neurodevelopment in Normocephalic Children Exposed to Zika Virus in Utero with No Observable Defects at Birth: A Systematic Review with Meta-Analysis.

Zika virus (ZIKV) infection during pregnancy is a cause of pregnancy loss and multiple clinical and neurological anomalies in children. This systematic review aimed to assess the effect of ZIKV exposure in utero on the long-term neurodevelopment of normocephalic children born to women with ZIKV infection in pregnancy. This review was conducted according to the PRISMA guidelines for systematic reviews and meta-analyses. We performed a random effects meta-analysis to estimate the cross-study prevalence of neurodevelopmental delays in children using the Bayley Scales for Infant and Toddler Development (BSID-III). The risk of bias was assessed using Cochrane's Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Full-text reviews were performed for 566 articles, and data were extracted from 22 articles corresponding to 20 studies. Nine articles including data from 476 children found 6.5% (95% CI: 4.1-9.3) of infants and children to have any type of non-language cognitive delay; 29.7% (95% CI: 21.7-38.2) to have language delay; and 11.5% (95% CI: 4.8-20.1) to have any type of motor delay. The pooled estimates had a high level of heterogeneity; thus, results should be interpreted with caution. Larger prospective studies that include a non-exposed control group are needed to confirm whether ZIKV exposure in utero is associated with adverse child neurodevelopmental outcomes.

Neighbors' use of water and sanitation facilities can affect children's health: a cohort study in Mozambique using a spatial approach.

BACKGROUND: Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection - community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children's morbidity and mortality using recorded health data. METHODS: We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012-2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality. RESULTS: Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition. CONCLUSION: Household and neighbors' access to improve water and sanitation can affect children's health. Accounting for household WASH and herd protection in interventions' evaluation could foster stakeholders' investment and improve WASH related diseases control. Distribution of main water and sanitation facilities used during study period.

Neighbors' use of water and sanitation facilities can affect children's health: a cohort study in Mozambique using a spatial approach

Background: Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection - community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children's morbidity and mortality using recorded health data. Methods: We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012-2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality. Results: Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition. Conclusion: Household and neighbors' access to improve water and sanitation can affect children's health. Accounting for household WASH and herd protection in interventions' evaluation could foster stakeholders investment and improve WASH related diseases control. Distribution of main water and sanitation facilities used during study period

Association of Clinical Signs, Host Biomarkers and Etiology With Radiological Pneumonia in Bhutanese Children.

Diagnosing pneumonia and identifying those requiring antibiotherapy remain challenging. Chest radiographs (CXR) are often used as the reference standard. We aimed to describe clinical characteristics, host-response biomarkers and etiology, and assess their relationship to CXR findings in children with pneumonia in Thimphu, Bhutan. Children between 2 and 59 months hospitalized with WHO-defined pneumonia were prospectively enrolled and classified into radiological endpoint and non-endpoint pneumonia. Blood and nasopharyngeal washing were collected for microbiological analyses and plasma levels of 11 host-response biomarkers were measured. Among 149 children with readable CXR, 39 (26.2%) presented with endpoint pneumonia. Identification of respiratory viruses was common, with no significant differences by radiological outcomes. No clinical sign was suggestive of radiological pneumonia, but children with radiological pneumonia presented higher erythrocyte sedimentation rate, C-reactive protein and procalcitonin. Markers of endothelial and immune activation had little accuracy for the reliable identification of radiological pneumonia.

Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care: a pilot cluster-randomized-controlled trial.

BACKGROUND: There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including human immunodeficiency virus (HIV), hepatitis B and C, active tuberculosis (TB), Chagas disease, strongyloidiasis and schistosomiasis, based on patient characteristics (including variables of country of origin, age and sex). METHODS: A pragmatic pilot cluster-randomized-controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on international standard randomised controlled trial number (ISRCTN) (ISRCTN14795012). RESULTS: A total of 15 780 migrants registered across the eight centres had at least one visit during the intervention period (March-December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group [odds ratio: 2.08, 95% confidence interval (CI) 1.63-2.64, P < 0.001]. The intervention centres raised their overall monthly diagnosis rate to 5.80 (95% CI 1.23-10.38, P = 0.013) extra diagnoses compared with the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases [2.72 (95% CI 0.43-5.00); P = 0.02] and was observed as well for the parasitic infections' group (Chagas disease, strongyloidiasis and schistosomiasis) 2.58 (95% CI 1.60-3.57; P < 0.001). CONCLUSIONS: The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries.

Initiation and adherence to isoniazid preventive therapy in children under 5 years of age in Manhiça, Southern Mozambique.

The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment.

Acute bronchiolitis and respiratory syncytial virus seasonal transmission during the COVID-19 pandemic in Spain: A national perspective from the pediatric Spanish Society (AEP).

INTRODUCTION AND OBJECTIVES: The COVID-19 pandemic and the widespread associated use of non-pharmaceutical interventions have impacted viral circulation and the incidence of respiratory tract infections. We compared Pediatric Emergency Department visits, bronchiolitis admissions, and respiratory syncytial virus (RSV) cases in 2020 with those documented for the preceding four years. METHODS: This was a retrospective multicentric national survey study, driven by the Pediatric Spanish Society, and gathering monthly data from Spanish hospitals between 1st January 2016 and 31st December 2020. An Interrupted Time Series Analysis and Poisson regression models were performed for each index. RESULTS: Thirty-eight hospitals representing most of the different regions of Spain participated. Compared to the preceding four years, in 2020, Pediatric emergency department visits significantly decreased immediately after initiation of the national lockdown. The median number of visits averted per month was 39,754 (IQR 26,539-50,065). RSV diagnoses during the 2020 winter season nearly disappeared with only 21 cases being documented among participating hospitals. The expected seasonal peak of bronchiolitis hospitalizations never occurred. The median number of admissions in 2020 averted per month was 100 (IQR 37-185) compared to 2016-2019. Only 3 hospitalized cases were RSV-confirmed. Reopening of schools and kindergarten was not associated with a remarkable increase in RSV cases or bronchiolitis hospitalizations. CONCLUSION: A dramatic reduction of bronchiolitis admissions and near disappearance of RSV cases was observed in Spanish hospitals coinciding with the peak of the COVID-19 pandemic.

Improved detection and management of advanced HIV disease through a community adult TB-contact tracing intervention with same-day provision of the WHO-recommended package of care including ART initiation in a rural district of Mozambique.

INTRODUCTION: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. METHODS: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/µL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. RESULTS: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. CONCLUSIONS: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.

Improved detection and management of advanced HIV disease through a community adult TB­contact tracing intervention with same­day provision of the WHO­recommended package of care including ART initiation in a rural district of Mozambique

Introduction: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. Methods: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/µL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. Results: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. Conclusions: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.