Snippets from the past: is Flint, Michigan, the birthplace of the case-control study?

In the summer of 1924, an outbreak of scarlet fever occurred in Flint, Michigan. Unable to trace it to the usual causes, particularly fresh milk, the Michigan Department of Health used a novel approach to disentangle the enigma: The 116 cases of scarlet fever were compared with 117 "controls" selected from neighbors of the quarantined cases and from patients at the City Health Center who had been treated for ailments unrelated to scarlet fever. The extraordinary culprit was ice cream, which had a frequent/occasional/none consumption prevalence of 60%, 34%, and 6% among the cases and 24%, 51%, and 25% among the controls, respectively. The 1925 report reads, "Detailed epidemiological investigation, by means of case histories and control histories on well persons, confirmed early suspicions and established the fact that the epidemic was spread by ice cream" (Am J Hyg. 1925;5(5):669-681). This forgotten epidemiologic study is the oldest study using the case-control design to have been resurrected thus far. The case-control study design may have been conceived simultaneously, but independently and for different purposes, in England (Janet Lane-Claypon's 1926 report on the determinants of breast cancer) and the United States.

Exposure to air pollution and scarlet fever resurgence in China: a six-year surveillance study.

Scarlet fever has resurged in China starting in 2011, and the environment is one of the potential reasons. Nationwide data on 655,039 scarlet fever cases and six air pollutants were retrieved. Exposure risks were evaluated by multivariate distributed lag nonlinear models and a meta-regression model. We show that the average incidence in 2011-2018 was twice that in 2004-2010 [RR = 2.30 (4.40 vs. 1.91), 95% CI: 2.29-2.31; p < 0.001] and generally lower in the summer and winter holiday (p = 0.005). A low to moderate correlation was seen between scarlet fever and monthly NO2 (r = 0.21) and O3 (r = 0.11). A 10 µg/m3 increase of NO2 and O3 was significantly associated with scarlet fever, with a cumulative RR of 1.06 (95% CI: 1.02-1.10) and 1.04 (95% CI: 1.01-1.07), respectively, at a lag of 0 to 15 months. In conclusion, long-term exposure to ambient NO2 and O3 may be associated with an increased risk of scarlet fever incidence, but direct causality is not established.

The Association between Environmental Factors and Scarlet Fever Incidence in Beijing Region: Using GIS and Spatial Regression Models.

(1) Background: Evidence regarding scarlet fever and its relationship with meteorological, including air pollution factors, is not very available. This study aimed to examine the relationship between ambient air pollutants and meteorological factors with scarlet fever occurrence in Beijing, China. (2) Methods: A retrospective ecological study was carried out to distinguish the epidemic characteristics of scarlet fever incidence in Beijing districts from 2013 to 2014. Daily incidence and corresponding air pollutant and meteorological data were used to develop the model. Global Moran's I statistic and Anselin's local Moran's I (LISA) were applied to detect the spatial autocorrelation (spatial dependency) and clusters of scarlet fever incidence. The spatial lag model (SLM) and spatial error model (SEM) including ordinary least squares (OLS) models were then applied to probe the association between scarlet fever incidence and meteorological including air pollution factors. (3) Results: Among the 5491 cases, more than half (62%) were male, and more than one-third (37.8%) were female, with the annual average incidence rate 14.64 per 100,000 population. Spatial autocorrelation analysis exhibited the existence of spatial dependence; therefore, we applied spatial regression models. After comparing the values of R-square, log-likelihood and the Akaike information criterion (AIC) among the three models, the OLS model (R² = 0.0741, log likelihood = -1819.69, AIC = 3665.38), SLM (R² = 0.0786, log likelihood = -1819.04, AIC = 3665.08) and SEM (R² = 0.0743, log likelihood = -1819.67, AIC = 3665.36), identified that the spatial lag model (SLM) was best for model fit for the regression model. There was a positive significant association between nitrogen oxide (p = 0.027), rainfall (p = 0.036) and sunshine hour (p = 0.048), while the relative humidity (p = 0.034) had an adverse association with scarlet fever incidence in SLM. (4) Conclusions: Our findings indicated that meteorological, as well as air pollutant factors may increase the incidence of scarlet fever; these findings may help to guide scarlet fever control programs and targeting the intervention.

[Staphylococcal toxic shock syndrome]. / Le syndrome de choc toxique staphylococcique.

The case of a 31 year old woman with staphylococcal toxic shock syndrome is reported. The usual clinical characteristics were found: it began during a menstrual period, and she presented with a state of shock, a high fever and a cutaneous eruption. Its evolution was marked by pulmonary interstitial oedema and acute renal failure requiring dialysis; the patient recovered but residual renal failure was still present four months later. A Staphylococcus aureus was isolated from vaginal, nasal and tracheal cultures. It produced enterotoxins A and F, which were responsible for the symptoms.

[Toxic staphylococcal cutaneous necrolysis (scalded skin syndrome) (author's transl)]. / Le syndrome toxique staphylococcique cutané dit des enfants ébouillantés (scalded skin syndrome).

The exfoliating exotoxin of serotype II staphylococci is responsable of three diseases with prevailing dermatologic symptoms: staphylococcal scarlet fever, staphylococcal Lyell syndrom and Ritter-Lyell disease. Melish demonstrated the effect of staphylococcal exotoxin on new-born mice less than five days old. This experimental model allowed to study the characteristics of the toxin. Precocious antistaphylococcal antibiotherapy is necessary.

[Role of various diseases of the upper respiratory tract in the epidemiological process of streptococcal infections]. / Znachenie nekotorykh zabolevanii verkhnikh dykhatel'nykh putei v epidemicheskom protsesse pri streptokokkovykh infektsiiakh.

Investigations conducted with the use of a specially elaborated method revealed a specific association of some (15--24%) of diseases diagnosed clinically as "acute respiratory affection" (ARA) with streptococcus infection. This was also confirmed by detection of an epidemiological association of ARA with scarlet fever revealed in some child collective bodies. The data obtained pointed to the definite role played by such diseases in the epidemic process in streptococcus infections.

Tonsillopharyngitis: clinical highlights.

Tonsillopharyngitis is an extremely common infection seen in adults and children. Although the symptoms and signs of this disease are usually sufficient to make a diagnosis, it is often difficult to make a distinction between bacterial and viral etiology on clinical grounds alone. The complications of tonsillopharyngitis may be classified into suppurative and nonsuppurative complications. The nonsuppurative complications include scarlet fever, acute rheumatic fever, and post-streptococcal glomerulonephritis. Suppurative complications include peritonsillar, parapharyngeal, and retropharyngeal cellulites and/or abscess. Features suggestive of viral bacterial (GABHS) etiologies, the medical and surgical guidelines for managing tonsillopharyngitis, and its complications are highlighted in this article.

Septic scarlet fever due to Streptococcus pyogenes cellulitis.

We report three cases of septic scarlet fever due to Streptococcus pyogenes Group A (serotype M1/T1/OF-) cellulitis in healthy young adults. Despite prompt treatment two of the patients died. Such cases of cellulitis associated with scarlet fever, severe toxaemia and septicaemia have not been reported in the post-antibiotic era.

A family outbreak of serious streptococcal infection.

A localized outbreak of scarlet fever was caused by an M-nontypable T-1 (NT/1) group A beta-hemolytic Streptococcus. The result was a fatal outcome in a 5-year-old child and a near fatality in his 10-year-old sibling. The outbreak was confined to family units that had members with whom the children were close playmates. Extensive epidemiologic studies in neighborhood schools and local hospital emergency rooms did not demonstrate a disemination of the causative serotype in the community.

Hypothesis--the natural selection of psoriasis.

The high genetic frequency of some inherited disorders may in part be related to a survival advantage conferred against an environmental hazard. Psoriasis is an inherited disorder which is common amongst populations of northern latitudes. Cutaneous delayed-type hypersensitivity response to streptococcal antigen is altered in such patients with a decrease in induration and erythema. Scarlet fever has until recently been associated with a high childhood mortality, the pathogenesis of which is related to interdependent primary toxicity and secondary toxicity (including delayed-type hypersensitivity) to streptococcal antigen (erythrogenic toxin), leading to cellular damage and potentially lethal shock. Streptococcal infection, usually presenting as pharyngitis, is a classical trigger for both scarlet fever and psoriasis. Individual susceptibility to scarlet fever has been clinically assessed in the past by the Dick test--an intradermal injection of the filtrate of a broth culture of scarlatina-producing strains of Streptococcus giving an erythematous reaction at 24-48 h (Dick-positive). The degree of reaction is directly related to susceptibility to scarlet fever. The severity of and mortality from scarlet fever may be ameliorated by immunological mechanisms also found in psoriatic patients. The high prevalence of psoriasis amongst some populations today may be related to such a protective factor.

Cutaneous manifestations of bacterial sepsis.

In short, bacterial sepsis is associated with a number of peripheral manifestations involving the skin and soft tissues. The pathogenesis of the lesions observed is not fully understood and is almost certainly multifactorial. In ecthyma gangrenosum, the presence of large numbers of gram-negative bacilli in the walls of small blood vessels without a substantial inflammatory response suggests that either the bacteria themselves or bacterial products are responsible for tissue damage. Endotoxin probably plays a prominent role in producing these lesions. That Pseudomonas and Aeromonas species seem to cause ecthyma out of proportion to their prevalence as a cause of bacteremia might suggest that the endotoxin of these organisms has a special predilection for skin and subcutaneous structures. More likely, it indicates that other bacterial substances, such as exotoxins or proteases, are involved. The absence of PMN leukocytes is thought to play a permissive role, allowing unopposed bacterial proliferation. Lesions of symmetric peripheral gangrene characteristically do not have bacteria present. The presence of intravascular fibrin accumulation probably resembles the generalized Shwartzman phenomenon. However, the gangrenous lesions themselves more likely result from systemic hypotension and the resulting hypoperfusion of the tissues than from vessel obstruction. In lesions associated with vigorous inflammatory response, bacterial products may damage tissue either directly or by attracting leukocytes that, in turn, release substances that cause further tissue damage. An etiologic role for endotoxin or the gram-positive bacterial cell wall is likely, since endotoxin is known to produce similar lesions in the localized Shwartzman reaction. Favoring a role for other bacterial substances is the predisposition of V. vulnificus to cause cellulitis or of C. fetus to cause inflammation of the major vessels during sepsis; the mechanisms for these reactions are entirely unknown. It is interesting that in most instances in which peripheral lesions are caused by sepsis, either a large number of bacteria or an intense inflammatory response by PMNs is present, but not both. In both kinds of lesion, the tendency to involve blood vessels by different pathogenetic mechanisms contributes to the evolution of the disease process. In intensely inflamed lesions, veins and arteries can be shown histologically to be occluded. In the absence of inflammation, bacterial invasion of vessel walls or simply the presence of bacterial products adjacent to the vessel may produce spasm. As noted, the pathogenetic significance of thrombosis observed in the lesions of DIC remains unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis.

BACKGROUND: We have previously demonstrated the preferential secretion of streptococcal proteinase or streptococcal pyrogenic exotoxin B (SPEB) by nephritic strains of Group A streptococci isolated from the skin or throat of patients with acute poststreptococcal glomerulonephritis (APSGN). METHODS: To further explore the possible role of SPEB in APSGN, we performed ELISA studies to detect anti-SPEB antibodies in the sera of patients with APSGN, acute rheumatic fever (ARF), scarlet fever (SF) and normal children. Using ELISA, anti-SPEB titers on acute and convalescent APSGN sera were measured to determine immunity to APSGN. We also performed immunofluorescence studies on APSGN and non-APSGN kidney biopsies to probe for the presence and localization of SPEB. RESULTS: Our data show that anti-SPEB antibodies are present in APSGN sera and antibody titers are significantly higher than in ARF, SF and normal sera. Anti-SPEB titers tend to rise acutely and decrease with time but do not reach baseline after one year. When kidney biopsies were probed with rabbit anti-SPEB antibody, 12 of 18 (67%) of the APSGN cases were positive while only 4 of 25 (16%) of the non-APSGN cases were positive. CONCLUSIONS: In summary, we were able to demonstrate unique reactivity to SPEB in human sera and kidney biopsies of APSGN suggesting a significant role of this toxin in the pathogenesis of acute post-streptococcal glomerulonephritis.

Reactivity of rheumatic fever and scarlet fever patients' sera with group A streptococcal M protein, cardiac myosin, and cardiac tropomyosin: a retrospective study.

Archived sera (collected in 1946) from acute rheumatic fever (ARF) and untreated scarlet fever and/or pharyngitis patients were reacted with streptococcal M protein, cardiac myosin, and cardiac tropomyosin. Except for very low levels to tropomyosin, antibodies to other antigens were not elevated in the sera of ARF patients relative to those of non-ARF patients, even though there was roughly equivalent exposure to group A streptococci. This suggests that antibodies to these molecules may not play a central role in the induction of ARF.

Penicillin for acute sore throat in children: randomised, double blind trial.

OBJECTIVE: To assess the effectiveness of penicillin for three days and treatment for seven days compared with placebo in resolving symptoms in children with sore throat. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: 43 family practices in the Netherlands. PARTICIPANTS: 156 children aged 4-15 who had a sore throat for less than seven days and at least two of the four Centor criteria (history of fever, absence of cough, swollen tender anterior cervical lymph nodes, and tonsillar exudate). Interventions Patients were randomly assigned to penicillin for seven days, penicillin for three days followed by placebo for four days, or placebo for seven days. MAIN OUTCOME MEASURES: Duration of symptoms, mean consumption of analgesics, number of days of absence from school, occurrence of streptococcal sequelae, eradication of the initial pathogen, and recurrences of sore throat after six months. RESULTS: Penicillin treatment was not more beneficial than placebo in resolving symptoms of sore throat, neither in the total group nor in the 96 children with group A streptococci. In the groups randomised to seven days of penicillin, three days of penicillin, or placebo, one, two, and eight children, respectively, experienced a streptococcal sequela. CONCLUSION: Penicillin treatment had no beneficial effect in children with sore throat on the average duration of symptoms. Penicillin may, however, reduce streptococcal sequelae.