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Background: Human Immunodeficiency Virus (HIV)-exposed and HIV-infected infants are at increased risk of vaccine-preventable diseases. However, little is known about health care workers’ knowledge and immunization counseling practices in this population. We determined the predictors of health care workers’ knowledge of vertical transmission risks, HIV exposed/infected infant immunization, and counseling practices in a tertiary center in Northern Nigeria. Methods: A cross-section of 297 health workers were interviewed using a structured, validated questionnaire. Knowledge and HIV-exposed infant immunization counseling practices were analyzed, and adjusted odds ratios for predictors were derived from logistic regression models. Results: Of the 297 participating health care workers, (32.3%, n=96) had adequate knowledge of HIVexposed/infected infant immunization. Two-thirds (67%, n=199) of the participants appropriately identified the timing of infant diagnosis, while (73%, n=217) and (56.2%, n=167) correctly categorized infants as HIV-exposed and HIV-infected, respectively. Only (19.5%, n=58) participants had ever counselled a HIVpositive mother on infant immunization. Knowledge was predicted by work unit (HIV clinic vs. Obstetrics & Gynecology clinic), (Adjusted Odds Ratio (AOR) =3.78, 95% CI: 1.27-5.54), age (30-39 vs.

Background Stunting and severe wasting can co-occur in under-fives, predisposing them to increased risks for morbidity and mortality. The Community Management of Acute Malnutrition (CMAM) programme, which provides outpatient malnutrition care for severely wasted children, has been successful at managing severe wasting, but there are limited data on stunting among entrants into these programmes. Methods We performed secondary analysis of data collected from attendees of two CMAM centres in north-western Nigeria. Using WHO reference standards, we determined the prevalence of concurrent stunting (height/length-for-age Results Our cohort comprised 472 severely wasted children and the majority (82.8%) were stunted. Age groups of 12–23 mo (adjusted OR [AOR]=2.38, 95% CI 1.26 to 4.48) and 24–35 mo (AOR=7.81, 95% CI 1.99 to 30.67), male gender (AOR=2.51, 95% CI 1.43 to 4.39) and attending the rural malnutrition clinic (AOR=3.08, 95% CI 1.64 to 5.79) were associated with a significantly increased probability of stunting. Conclusions Stunting prevalence is high among severely wasted children attending CMAM programmes in north-western Nigeria. Policymakers need to adapt these treatment programmes to also cater for stunting, taking into account practical programmatic realities such as available expertise and scarce resource allocation.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertensió gestacional; Preeclampsia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hipertension gestacional; Preeclampsia Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Gestational hypertension; Preeclampsia Background It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19. The study was supported by the COVID-19 Research Response Fund from the University of Oxford (Ref 0009083). A.T.P. is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the National Institute for Health Research (NIHR) Biomedical Research Centre funding scheme. The funding organization had no involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

Supplemental Digital Content is available in the text., IMPORTANCE: Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES: To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS: A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES: Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS: Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS: Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

BackgroundSevere acute malnutrition (SAM) is associated with significant morbidity and mortality and is disproportionately distributed mainly in developing countries. In Nigeria, the prevalence of SAM in the North-Western region of the country is significantly higher than the national average. In this study, we identified risk factors for SAM in North-Western Nigeria. Identifying such risk factors would be helpful in developing local preventive strategies and providing insights for broader SAM control programs in other high-burden country settings.MethodsWe performed post hoc data analysis, comparing baseline socio-demographic and household-level risk factors in a cohort of 1011 children aged between 6 and 59 months who either had SAM or were well-nourished children. We defined nutritional status using the World Health Organization (WHO) reference standards and investigated the association between SAM and our identified risk factors using multivariable logistic regression model.ResultsChildren aged between 12 and 23 months [adjusted odds ratio (AOR) 2.95, 95% confidence interval (CI) 1.99–4.38], household who reared domestic animals (AOR 1.94, 95% CI 1.40–2.69) and those from polygamous households (AOR 1.91, 95% CI 1.33–2.74) had significantly increased odds of developing SAM. Parental education and being on the household diet reduced the odds of having SAM.ConclusionsOur findings suggest the need to develop optimal complementary feeding nutrition programs and promote adult and general education in our community. Cultural and feeding practices in local polygamous households also need further investigation to understand the association between polygamy with SAM.

Nearly 7% of the world’s population lives with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.

Supplemental Digital Content is available in the text., IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

BackgroundBacteremia is a leading cause of mortality in developing countries, however, etiologic evaluation is infrequent and empiric antibiotic use not evidence-based. Here, we evaluated the patterns of ESBL resistance in children enrolled into a surveillance study for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria.MethodBlood culture was performed for children aged less than 5 years suspected of having sepsis from Sept 2008-Dec 2016. Blood was incubated using the BACTEC00AE system and Enterobacteriacea identified to the species level using Analytical Profile Index (API20E®). Antibiotic susceptibility profile was determined by the disc diffusion method. Real time PCR was used to characterize genes responsible for ESBL production.ResultOf 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413 Enterobacteriaceae available for analysis were screened for ESBL. ESBL production was detected in 160 Enterobacteriaceae, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.3%), Cefotaxime (98.8%) and Trimethoprim/sulfamethoxazole (90%), while 87.5%, 90.7%, and 91.9% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes were blaTEM-83.8% (134/160), and, blaCTX-M 83.1% (133/160) followed by blaSHVgenes 66.3% (106/160). Co-existence of blaCTX-M, blaTEM and blaSHV was seen in 94/160 (58.8%), blaCTX-M and blaTEM in 118/160 (73.8%), blaTEM and blaSHV in 97/160 (60.6%) and blaCTX-M and blaSHV in 100/160 (62.5%) of isolates tested.ConclusionOur results indicate a high prevalence of bacteremia from ESBL Enterobacteriaceae in this population of children. These are resistant to commonly used antibiotics and careful choice of antibiotic treatment options is critical. Further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.

Caregiver satisfaction has the potential to promote equity for children living with HIV, by influencing health-seeking behaviour. We measured dimensions of caregiver satisfaction with paediatric HIV treatment in Nigeria, and discuss its implications for equity by conducting facility-based exit interviews for caregivers of children receiving antiretroviral therapy in 20 purposively selected facilities within 5 geopolitical zones. Descriptive analysis and factor analysis were performed. Due to the hierarchical nature of the data, multilevel regression modelling was performed to investigate relationships between satisfaction factors and socio-demographic variables. Of 1550 caregivers interviewed, 63% (95% CI: 60.6–65.4) reported being very satisfied overall; however, satisfaction varied in some dimensions: only 55.6% (53.1–58.1) of caregivers could talk privately with health workers, 56.9% (54.4–59.3) reported that queues to see health workers were too long, and 89.9% (88.4–91.4) said that some health workers did not treat patients living with HIV with sufficient respect. Based on factor analysis, two underlying factors, labelled Availability and Attitude, were identified. In multilevel regression, the satisfaction with availability of services correlated with formal employment status (p

Objectives Acute febrile illness is a common cause of hospital admission, and its associated infectious causes, of which a key bacterial causative agent is Streptococcus pneumoniae, contribute to substantial morbidity and mortality. We sought to evaluate the utility of real-time (rt)-PCR on dried blood spots (DBS) for diagnosis of S. pneumoniae in acute febrile illness among children presenting to hospitals in Nigeria. We previously described preliminary results in a sample of 537 patients. Here we present data from a larger collection of 1038 patients. Results Using rt-PCR for Streptococcus pneumoniae on 1038 dried blood spots from children prospectively enrolled with acute febrile illness, including 79 healthy controls, we detected pneumococcal DNA in nine of 15 blood culture-positive specimens, one culture-negative specimen from a high-risk group, a culture-confirmed non-pneumococcal specimen and a healthy control. Six culture-positive isolates (40%) were negative. Sensitivity was 60%, specificity 99.7%, positive predictive value 75% and negative predictive value 99.4%. Rt-PCR of DBS has limited sensitivity in blood specimens from acute febrile illness in children.

Background Soil-transmitted helminthic (STH) infections are common in Sub-Saharan Africa. One method used for control of these helminths is mass anti-helminthic administration in populations at risk of STH infections. In this regard, empiric treatment of children with Severe Acute Malnutrition (SAM) for STH infection is practiced in this region. It is however unclear if children with SAM suffer more from STH infection than healthy children. The objective of this study was to compare prevalence and intensity of STH infection between pre-school aged children with SAM and healthy children. Methods We approached 1114 pre-school aged children attending care in two health facilities in Kano, Nigeria to partake in this study. Of this number, we recruited 620 (55.7%) children, comprising 310 well-nourished children from well-baby clinics and 310 children with SAM from Community Management for Acute Malnutrition (CMAM) centres in these facilities. We assessed their nutritional status using World Health Organisation (WHO) growth charts and collected stool samples which we analysed using Formal-Ether Concentration technique to identify STH infection and Stoll’s technique to assess intensities of STH infection. We fitted a logistic regression model to determine if there was any association between nutrition status and helminthic infection, adjusting for the confounding effects of socio-economic status and age. We compared intensity of STH infection (measured as eggs per gram of faeces) between both nutrition groups using the independent t-test. Results Overall STH prevalence in our population was low (2.7%) and we found no significant association between nutritional status and presence of STH infection (OR = 1.10, 95% CI 0.38 to 3.21). Majority of our study participants had either low or moderate (94.2%) and there was no statistically significant difference between intensity of STH infection (t value = − 1.52, P value = 0.13) in children with SAM and those who were well-nourished. Conclusions The overall STH prevalence among pre-school children was low in Kano and we did not find prevalence and intensity of STH infection to differ significantly between preschool children with SAM and well-nourished children. Our findings confirm the WHO recommendation that at low levels of prevalence and intensity, interventions to control STH are unnecessary.

Background. Etiologic agents of childhood bacteremia remain poorly defined in Nigeria. The absence of such data promotes indiscriminate use of antibiotics and delays implementation of appropriate preventive strategies. Methods. We established diagnostic laboratories for bacteremia surveillance at regional sites in central and northwest Nigeria. Acutely ill children aged

Adherence to artemisinin-based combination therapy (ACT) is not clearly defined. This meta-analysis determines the prevalence and predictors of adherence to ACT. Twenty-five studies and six substudies met the inclusion criteria. The prevalence of ACT adherence in the public sector was significantly higher compared to retail sector (76% and 45%, resp.,P<0.0001). However, ACT adherence was similar across different ACT dosing regimens and formulations. In metaregression analysis prevalence estimates of adherence significantly decrease with increasing year of study publicationP=0.046. Factors found to be significant predictors of ACT adherence were years of education ≥ 7{odds ratio (OR) (95% CI) = 1.63 (1.05–2.53)}, higher income{2.0 (1.35–2.98)}, fatty food{4.6 (2.49–8.50)}, exact number of pills dispensed{4.09 (1.60–10.7)}, and belief in traditional medication for malaria{0.09 (0.01–0.78)}. The accuracy of pooled estimates could be limited by publication bias, and differing methods and thresholds of assessing adherence. To improve ACT adherence, educational programs to increase awareness and understanding of ACT dosing regimen are interventions urgently needed. Patients and caregivers should be provided with an adequate explanation at the time of prescribing and/or dispensing ACT.

Improved serodiagnostic tests for typhoid fever (TF) are needed for surveillance, to facilitate patient management, curb antibiotic resistance, and inform public health programs. To address this need, IgA, IgM and IgG ELISAs using Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS) and hemolysin E (t1477) protein were conducted on 86 Nigerian pediatric TF and 29 non-typhoidal Salmonella (NTS) cases, 178 culture-negative febrile cases, 28 “other” (i.e., non-Salmonella) pediatric infections, and 48 healthy Nigerian children. The best discrimination was achieved between TF and healthy children. LPS-specific IgA and IgM provided receiver operator characteristic areas under the curve (ROC AUC) values of 0.963 and 0.968, respectively, and 0.978 for IgA+M combined. Similar performance was achieved with t1477-specific IgA and IgM (0.968 and 0.968, respectively; 0.976 combined). IgG against LPS and t1477 was less accurate for discriminating these groups, possibly as a consequence of previous exposure, although ROC AUC values were still high (0.928 and 0.932, respectively). Importantly, discrimination between TF and children with other infections was maintained by LPS-specific IgA and IgM (AUC = 0.903 and 0.934, respectively; 0.938 combined), and slightly reduced for IgG (0.909), while t1477-specific IgG performed best (0.914). A similar pattern was seen when comparing TF with other infections from outside Nigeria. The t1477 may be recognized by cross-reactive antibodies from other acute infections, although a robust IgG response may provide some diagnostic utility in populations where incidence of other infections is low, such as in children. The data are consistent with IgA and IgM against S. Typhi LPS being specific markers of acute TF., Author summary In many African countries, clinical management of children that present with symptoms of bacterial sepsis, such as typhoid fever (TF) caused by Salmonella Typhi, consists of empiric broad spectrum antibiotics. Blood culture remains the gold-standard for diagnosis, but is slow, suffers from poor sensitivity, and often unavailable. Consequently multi-drug resistant bacteria have emerged that are difficult to manage with antibiotics. There is an urgent need to develop rapid, sensitive and affordable tests for patient diagnosis, help curb antibiotic resistance, and inform public health preventive strategies such as the deployment of vaccines. Here, we have assessed antibodies to S. Typhi lipopolysaccharide (LPS) and hemolysin E (HylE, t1477) in the sera of Nigerian children with acute TF and compared them with heathy children, children with other febrile infections, and adults from around the world with a variety of other bacterial infections. The key finding concerns LPS. This is a common cell-wall component present in many bacterial species. Yet despite this, S. Typhi LPS-specific IgA and IgM are excellent markers of acute TF in Nigerian children, and insensitive to other non-salmonelloses. This surprising finding suggests a rapid point-of-care test for TF can be developed based on detection of LPS-specific IgA+IgM.

Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. Homozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings. References: 1. Weatherall DJ, Clegg JB. Bull World Health Organ. 2001;79(8):704-712. 2. Mburu J, Odame I. International Journal of Laboratory Hematology. 2019;41(S1):82-88. 3. Alapan Y, Fraiwan A, Kucukal E, et al. Expert Review of Medical Devices. 2016;13(12):1073-1093. 4. Bossuyt PM, Reitsma JB, Bruns DE, et al. BMJ : British Medical Journal. 2015;351:h5527. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Piccone:Hemex Health, Inc.: Patents & Royalties. Little:Hemex Health, Inc.: Patents & Royalties; GBT: Research Funding. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

Nigeria leads the world in the number of cases of sickle cell disease (SCD). An estimated 150,000 babies are born annually in Nigeria with SCD, a heredity disorder, and 70-90% die before age 5. Only a small portion of affected infants and children in sub Saharan Africa (SSA) reach adolescence. Over 650 children die per day in sub-Saharan Africa from SCD. These dismal statistics are in sharp contrast to outcomes in high-income countries (HICs) where more than 90% of SCD patients reach adulthood. The World Health Organization (WHO) estimates that 70% of deaths could be prevented with a low cost diagnostic and treatment plan. Meaningful preventive care and treatment cannot be implemented without a structured plan for early diagnosis and patient tracking.Early diagnosis requires improved access to parents and guardians of children with SCD, and gaining this access remains a challenge in most of SSA. In 2015, Nigeria's Kano state government, with support from foreign partners, established a community-based program for newborn registration. This platform provides unique access to newborn babies in one of Nigeria's most populous cities, but still lacks a functioning patient testing, tracking, and monitoring system, which we plan to address in our ongoing study. This study will introduce mobile health in a low-income country with low literacy rate and hopefully accustom that segment of the population to more varied mobile health applications that will ultimately improve their health in the long run. Our current operational platform in Kano, Nigeria provides access to a large population with a high prevalence of SCD. We have previously completed pilot testing of 315 subjects for SCD using our microchip electrophoresis test. We are planning to test up to 4,500 additional subjects less than 5 years of age at Murtala Muhammed Specialist Hospital. The hospital staff includes 97 physicians and 415 nurses and outpatient clinics serve about 30,000 patients monthly. The maternity department has a 200-bed capacity and the antenatal clinic performs about 1,000 deliveries and serves an average of 3,000 mothers monthly. Enrollment is planned to start on September 15, 2019 and medical staff are currently being trained to run the tests. Our study is registered in the United States National Library of Medicine's ClinicalTrials.gov (Identifier: NCT03948516). Our technology is uniquely paired with an automatic reader and an Electronic Medical Record (EMR) and patient management solution to record POC test results, register new cases, and track patients for follow-up (Fig. 1). The reader enables automated interpretation of test results, local and remote test data storage, and includes geolocation (Global Positioning System) (Fig. 2). The system will generate reports for all cases of SCD, track hospital visits, appointments, lab tests, and will have mobile and dashboard applications for tracking patients and samples. The application will be installed on mobile devices provided to users. The proposed system will be compliant with the existing privacy standards to handle medical data (e.g., HIPAA in the US and GDPR in the EU). All communications between the parties will be secured via end-to-end encryption as a safeguard. We anticipate that our project will increase the rates of screening, diagnosis and timely treatment of SCD in Kano State of Nigeria. The project's broader impact will likely be the ability to track and monitor screening, disease detection, diagnosis and treatment, which can be scaled up to the whole nation of Nigeria, then to sub-Saharan Africa. The data obtained and analyzed will be the first of their kind and will be used to inform the design of programs to improve access to, and availability of, effective care for this underserved populations. The importance of increased access to diagnosis and treatment should not be underestimated - it is crucial for realizing effective management of people with SCD. The impact can be enhanced by complementing diagnosis and patient tracking with education for the families so they can provide or seek the necessary preventative treatment. Identification of the location of the patients in need would help identify the areas where family, parent, caregiver education should be provided. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

In sub-Saharan Africa, nearly a quarter of a million babies are born with sickle cell disease (SCD) each year. An estimated 50-90% of these babies die before age 5 due to lack of early diagnosis and timely treatment. The World Health Organization estimates that more than 70% of SCD related deaths are preventable with simple, cost-effective interventions, such as early screening followed by affordable and widely available treatment regimens. Here, we present the early clinical testing results of HemeChip, which is the first single-use cartridge-based microchip electrophoresis hemoglobin screening platform. HemeChip was developed by Hemex Health, Inc., based on technology licensed from Case Western Reserve University. HemeChip allows affordable, objective, quantitative screening of hemoglobin variants at the point-of-care. HemeChip works with a drop of finger or heel-prick blood and separates hemoglobin variants on a piece of cellulose acetate paper that is housed in an injection molded plastic cartridge with a precisely controlled electric field. HemeChip works with a portable reader to produce easily understandable, objective, and quantitative descriptions of the hemoglobin types and percentages present in a blood sample. The HemeChip reader guides the user step-by-step through the test procedure with animated on-screen instructions to minimize user errors. Hemoglobin identification and quantification is automatically done with a custom software on the reader. HemeChip reader records and analyzes the hemoglobin electrophoresis real-time, and it can wirelessly transmit the test results to a central electronic database, if needed. HemeChip prototype units have been clinically tested and benchmarked against the clinical standard technique in Kano, Nigeria, where the SCD prevalence is the highest in the world. We tested a total of 248 subjects (228 children aged 6 weeks to 5 years in Kano, Nigeria; and 20 adults in Cleveland, Ohio, United States) under institutional review board approval, using both HemeChip and the clinical standard laboratory method, High Performance Liquid Chromatography (HPLC, VARIANT™ II, Bio-Rad Laboratories, Inc., Hercules, California). HemeChip tests were done on eHealth Africa campus in Kano, Nigeria, by trained local healthcare workers using blood samples collected at the nearby Aminu Kano Teaching Hospital. Clinical standard (HPLC) testing was done independently by the International Foundation Against Infectious Disease in Nigeria (IFAIN, Abuja, Nigeria) for the blood samples obtained in Kano or by the University Hospitals Cleveland Medical Center Clinical Laboratories (Cleveland, Ohio) for the blood samples obtained in Cleveland. Test results included the following: homozygous SCD (HbSS), heterozygous sickle hemoglobin C disease (HbSC), heterozygous sickle trait (HbAS), and normal (HbAA). HemeChip identified the subjects with HbSS with 100% accuracy, HbSC with 100% accuracy, HbAS with 98.2% accuracy, and HbAA with 96.4% accuracy in comparison to HPLC (Table 1). Overall accuracy of HemeChip was 97.2% in comparison to HPLC for the subjects tested. HemeChip sensitivity was 100% for all hemoglobin variants tested (Table 2), and specificity was 96.4% for HbSS vs. HbAA, 98.2% for HbSS vs. HbAS, 100% for HbSC vs. HbAS, and 100% for HbAS vs. HbAA. Bland-Altman analysis indicated strong agreement between the quantitative HPLC and HemeChip results for hemoglobin percentages, with a mean bias of -3.2%. HemeChip enables, for the first time, accurate, cost-effective identification and quantification of hemoglobin variants at the point-of-need. HemeChip has been developed based on a versatile, mass-producible microchip electrophoresis platform technology that may address other unmet needs in biology and medicine that require rapid, decentralized hemoglobin or protein analysis, identification, and/or quantification. Disclosures Thota: Hemex Health Inc: Employment. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding; Doris Duke Charitable Foundations: Research Funding.

Microalbuminuria has been reported to be a precursor of HIV related renal disease, which if detected early and coupled with appropriate intervention may slow or retard the progress of the disease. One hundred and seventy-eight HIV infected children aged 15 years and below were recruited from the Paediatric Infectious Disease Clinic of Aminu Kano Teaching Hospital (AKTH), Kano, to determine the prevalence of persistent microalbuminuria using the albumin creatinine ratio (ACR). Early morning urine samples and spot urine samples were analyzed using a dipstick specific for microalbumin. Those who tested positive had their samples reanalyzed in the laboratory using immunometric assay and Jaffe reaction method for albumin and creatinine, respectively. Patients that had ACR of 30–300 mg/g were said to have microalbuminuria and had their urine samples retested after 6 to 8 weeks. Twelve children (6.7%) had persistent microalbuminuria and had a mean age of years, with a male to female ratio of 1 : 1. There was no significant relationship between the finding of microalbuminuria and age, sex, duration of infection, and the use of highly active antiretroviral therapy. Periodic screening for microalbuminuria using albumin specific dipstick should be considered for children with HIV infection.