Measles surveillance--United States, 1991.

A total of 9,643 measles cases was reported from the United States in 1991, a 65.3% decrease from the 27,786 cases reported in 1990. The overall incidence of measles was 3.9 cases per 100,000 population. The highest age-specific incidence was among children < 12 months of age (46.9/100,000) and 1-4 years of age (19.6/100,000). Incidence rates among American Indians, Hispanic, and black children < 5 years of age were 19, 6, and 4 times that for non-Hispanic white children, respectively. More than 61% of all cases were reported from seven large outbreaks, which involved predominantly unvaccinated preschool-age children in large urban areas. Although reported measles cases decreased in 1991 compared with 1989-1990, only a sustained effort to provide age-appropriate vaccination will prevent another resurgence of measles.     

Using clinical signs to diagnose anaemia in African children.

Anaemia is a serious and common problem among young children in sub-Saharan Africa. As a first step towards developing guidelines for its recognition and treatment, we conducted a study to evaluate the ability of health workers to use clinical findings to identify children with anaemia. Health care workers examined a total of 1104 children under 5 years of age at two hospital-based outpatient clinics in rural Malawi. Blood samples were taken to determine haemoglobin concentrations. Pallor of the conjunctiva, tongue, palm or nail beds was 66% sensitive and 68% specific in distinguishing children with moderate a anaemia (haemoglobin concentration, 5-8 g/dl) and 93% sensitive and 57% specific in distinguishing those with severe anaemia (haemoglobin concentration, < 5 g/dl). Even without laboratory support, which is often unavailable in rural Africa, clinical findings can identify the majority of children with anaemia.     

Genetic evidence on the origins of Indian caste populations

The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (approximately 600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.     

Reperfusion arrhythmias during coronary reperfusion therapy in man. Clinical and angiographic correlations

We hypothesized that patients suffering acute myocardial infarction who have reperfusion arrhythmias (RPA) during intracoronary streptokinase infusion (ICSK) would have different clinical and angiographic characteristics and a larger infarction size than those who achieved reperfusion without RPA. Of 35 patients who received intracoronary streptokinase, 27 had successful reperfusion documented by angiography. Successful reperfusion was accompanied by RPA in eight patients and no RPA in 19 patients. RPA included episodes of ventricular tachycardia in one, idioventricular rhythm in four, junctional bradycardia in one, or AV block in two patients which occurred at the time of reperfusion. Myocardial infarction size was calculated using creatine kinase-MB (CK-MB) isoenzyme time activity curves using standard methods. The mean CK-MB g equivalents (eq) for those with RPA was 71 +/- 25 (+/- 1 SD) and for those with no RPA was 45 +/- 24 (p less than .04). In patients with RPA, ejection fraction rose 5 +/- 14 percentage points before discharge, but fell 10 +/- 13 points in those with RPA (p less than .03). There was no difference between groups in total dose of streptokinase, final degree of stenosis of the affected vessel, reocclusion rate, or time from onset of symptoms to reperfusion. We conclude that patients suffering acute myocardial infarction who have RPA during ICSK in most cases have a larger infarction site or a more "stunned myocardium," as indicated by greater CK-MB release and fall in ejection fraction which is not due to increased time of ischemia.     

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.     

Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001

STUDY OBJECTIVES: COPD is one of the leading causes of mortality and morbidity in the United States, yet little is known about the prevalence of comorbid conditions and mortality in hospitalized patients with COPD. DESIGN: From the National Hospital Discharge Survey, 1979 to 2001, we evaluated whether or not COPD in adults > or = 25 years old is associated with increased prevalence and in-hospital mortality of several comorbidities. RESULTS: During 1979 to 2001, there were an estimated total of 47,404,700 hospital discharges (8.5% of all hospitalizations in adults > 25 years old) of patients with COPD; 37,540,374 discharges (79.2%) were made with COPD as a secondary diagnosis, and 9,864,278 discharges (20.8%) were made with COPD as the primary diagnosis. The prevalence and in-hospital mortality for pneumonia, congestive heart failure, ischemic heart disease, thoracic malignancies, and respiratory failure were larger in hospital discharges with any mention of COPD. CONCLUSIONS: In a nationally representative sample of hospitalizations, any mention of COPD in the discharge diagnosis is associated with higher hospitalization prevalence and in-hospital mortality from other comorbidities. These results highlight the fact that the burden of disease associated with COPD is likely underestimated.     

Independent value of signal-averaged electrocardiography and left ventricular function in identifying patients with sustained ventricular tachycardia with coronary artery disease

To determine if the signal-averaged electrocardiographic detection of late potentials is an independent marker of sustained ventricular tachycardia (VT) in patients with documented chronic coronary artery disease (CAD), 57 patients underwent signal-averaged electrocardiography. Mean ejection fraction was 47 +/- 13% in the 14 patients with sustained VT and 56 +/- 19% in the 43 patients without VT (difference not significant). The sensitivity, specificity and accuracy of late potentials for detecting patients with VT were 64% (9 of 14), 79% (34 of 43), and 75% (43 of 57), respectively. Univariate analysis and stepwise logistic regression of angiographic and electrocardiographic variables identified late potentials as an independent marker of the patient with sustained VT. The odds ratio for late potentials to detect patients with prior sustained VT was 2.6. Six-month follow-up revealed a cardiac mortality rate of 11% and an arrhythmia event rate of 22% in patients with late potentials vs a cardiac mortality rate of 3% and an arrhythmia event rate of 13% in patients without late potentials. Thus, signal-averaged electrocardiographic detection of late potentials is useful in identifying patients with prior sustained VT independent of left ventricular function.