Abstract
In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 62%) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive ...predictive value (83% 95% confidence interval CI, 55%–95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.
Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible ...PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes.
We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% 95% CI: 12%-55%) was significantly lower than among persons aged ≥15 years (72% 95% CI: 47%-89%; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% 95% CI: 49%-87%). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART.
Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.
We assessed tuberculosis (TB) diagnostic delays among patients with TB and COVID-19 in California, USA. Among 58 persons, 43% experienced TB diagnostic delays, and a high proportion (83%) required ...hospitalization for TB. Even when viral respiratory pathogens circulate widely, timely TB diagnostic workup for at-risk persons remains critical for reducing TB-related illness.
Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus ...disease 2019.
We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts (<18 years), we described transmission, assessed the risk factors for infection, and calculated symptom positive and negative predictive values. We compared secondary infection rates and symptoms between pediatric and adult contacts using generalized estimating equations.
Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval CI: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio OR: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18).
Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.
Early detection of leptospirosis with field-ready diagnostics may improve clinical management and mitigate outbreaks. We previously validated the point-of-care Dual Path Platform (DPP) for ...leptospirosis with sera in the laboratory. This prospective study compares the diagnostic accuracy and clinical utility of the DPP using finger stick blood (FSB) against the serum DPP, venous whole blood (VWB) DPP, IgM-ELISA, and clinical impression. We sequentially enrolled 98 patients hospitalized for acute febrile illnesses, of which we confirmed 32 by leptospirosis reference tests. Among syndromes consistent with classic leptospirosis, the FSB DPP showed similar sensitivity and specificity (Se 93% and Sp 80%), and positive and negative predictive values (PPV 74% and NPV 95%), to VWB DPP (Se 96%, Sp 75%, PPV 68%, and NPV 97%), serum DPP (Se 85%, Sp 87%, PPV 79%, and NPV 91%) and IgM-ELISA (Se 81%, Sp 100%, PPV 100%, and NPV 90%). The FSB DPP provided a favorable likelihood ratio profile (positive LR 4.73, negative LR 0.09) in comparison to other assays and clinical impression alone. Additionally, we identified four of five leptospirosis-associated meningitis patients by whole blood DPP, none of which clinicians suspected. This demonstrates potential for the DPP in routine detection of this less common syndrome. The FSB DPP demonstrated similar discrimination for severe human leptospirosis compared with serum assays, and it is a simpler option for diagnosing leptospirosis. Its performance in other epidemiological settings and geographic regions, and for detecting atypical presentations, demands further evaluation.
While studying aseptic meningitis in Salvador, Brazil, we diagnosed anicteric leptospirosis in 1.7% (5/295) of patients hospitalized for aseptic meningitis. Leptospirosis-associated meningitis ...patients had lower mean cerebrospinal fluid cell counts and protein than other-cause aseptic meningitis (p<0.05). Clinicians must consider leptospirosis-associated meningitis in appropriate clinical-epidemiologic contexts.
Brazil's National STD/AIDS Program is considered a model of success worldwide. However, AIDS-associated malnutrition continues in subgroups of Brazilian patients despite access to free highly active ...antiretroviral therapy (HAART). We aimed to identify the prevalence of malnutrition and associated factors among patients hospitalized with AIDS.
We conducted a cross-sectional nutritional assessment among 127 adults hospitalized with AIDS in Brazil's third largest city. Using anthropometric measurements, we determined the prevalence of malnutrition (body mass index <18.5 kg/m2) at hospitalization. Prevalence ratios of malnutrition by demographic, socioeconomic, and clinical conditions were estimated using log-binomial regression.
One-third of participants were first informed of their HIV disease during the current hospitalization and recent treatment interruption was common (71%) among those on HAART. Forty-three percent were malnourished and 35% had severe weight loss at admission. Patient characteristics independently associated with malnutrition were older age (2% increased prevalence for each year; 95% confidence interval CI 0-4%) and very low daily per capita household income. Living on <USD 2.00, USD 2.00-4.99 or USD 5.00-9.99 increased the prevalence of malnutrition by 2.01 (95% CI 1.06-3.81), 1.75 (95% CI 0.92-3.35) and 1.42 (95% CI 0.76-2.65) times, respectively, compared to ≥USD 10.00 per day. Chronic diarrhea was marginally associated with malnutrition (RR 1.42; 95% CI 0.99-2.04). Overall, 16% of the patients died during hospitalization. We observed a trend toward higher in-hospital case fatality among malnourished patients (22% vs. 12% for patients with and without malnutrition, respectively; chi square P = 0.14).
Unacceptably high rates of malnutrition persist in Brazilians hospitalized with AIDS and our results reinforce the importance of nutritional evaluations in these patients. Improved early testing and treatment adherence strategies may continue to help reduce AIDS-related morbidity and mortality in Brazil, yet novel interventions to disrupt the cycle of poverty, HIV, and malnutrition are also urgently needed.
Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 ...within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB–COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 95% CI 0.8‒1.4). Among TB–COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB–COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.
Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control.
We assessed diagnostic ...performance of existing cases definitions (e.g. influenza-like illness, COVID-like illness) using symptoms reported from 185 household contacts to a PCR-confirmed case of COVID-19 in Wisconsin and Utah, United States. We stratified analyses between adults and children. We also constructed novel case definitions for comparison.
Existing COVID-19 case definitions generally showed high sensitivity (86-96%) but low positive predictive value (PPV) (36-49%; F-1 score 52-63) in this community cohort. Top performing novel symptom combinations included taste or smell dysfunction and improved the balance of sensitivity and PPV (F-1 score 78-80). Performance indicators were generally lower for children (< 18 years of age).
Existing COVID-19 case definitions appropriately screened in household contacts with COVID-19. Novel symptom combinations incorporating taste or smell dysfunction as a primary component improved accuracy. Case definitions tailored for children versus adults should be further explored.
Diagnosis of leptospirosis by the gold standard serologic assay, the microscopic agglutination test (MAT), requires paired sera and is not widely available. We developed a rapid assay using ...immunodominant Leptospira immunoglobulin-like (Lig) proteins in a Dual Path Platform (DPP). This study aimed to evaluate the assay's diagnostic performance in the setting of urban transmission.
We determined test sensitivity using 446 acute and convalescent sera from MAT-confirmed case-patients with severe or mild leptospirosis in Brazil. We assessed test specificity using 677 sera from the following groups: healthy residents of a Brazilian slum with endemic transmission, febrile outpatients from the same slum, healthy blood donors, and patients with dengue, hepatitis A, and syphilis. Three operators independently interpreted visual results without knowing specimen status.
The overall sensitivity for paired sera was 100% and 73% for severe and mild disease, respectively. In the acute phase, the assay achieved a sensitivity of 85% and 64% for severe and mild leptospirosis, respectively. Within seven days of illness onset, the assay achieved a sensitivity of 77% for severe disease and 60% for mild leptospirosis. Sensitivity of the DPP assay was similar to that for IgM-ELISA and increased with both duration of symptoms (chi-square regression P = 0.002) and agglutinating titer (Spearman ρ = 0.24, P<0.001). Specificity was ≥93% for dengue, hepatitis A, syphilis, febrile outpatients, and blood donors, while it was 86% for healthy slum residents. Inter-operator agreement ranged from very good to excellent (kappa: 0.82-0.94) and test-to-test reproducibility was also high (kappa: 0.89).
The DPP assay performed acceptably well for diagnosis of severe acute clinical leptospirosis and can be easily implemented in hospitals and health posts where leptospirosis is a major public health problem. However, test accuracy may need improvement for mild disease and early stage leptospirosis, particularly in regions with high transmission.
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