Jairam R. Lingappa

Outbreak of Leptospirosis among Triathlon Participants and Community Residents in Springfield, Illinois, 1998

We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 µg/mL, a reliable lower limit of detection of 0.09 µg/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 µg/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 94.2%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

Risk factors for bronchiolitis-associated deaths among infants in the United States

Background. Risk factors for bronchiolitis deaths have not been described on a national level. We examined the epidemiology of and identified risk factors for bronchiolitis-associated deaths among infants in the United States. Methods. Multiple cause-of-death and linked birth/infant death data for 1996 through 1998 were used to examine bronchiolitis-associated infant deaths. Risk factors were assessed by comparing infants who died with bronchiolitis and surviving infants. Results. During 1996 through 1998 there were 229 bronchiolitis infant deaths, resulting in an average annual infant mortality rate of 2.0 per 100 000 live births. The majority (55%) of infant deaths occurred among infants ages 1 through 3 months. The bronchiolitis mortality rate was highest among infants weighing <1500 g at birth (VLBW) as compared with infants weighing 1500 to 2499 g (LBW) and ≥2500 g at birth (29.8, 6.4 and 1.3 per 100 000 live births, respectively). Sixty-three percent of bronchiolitis deaths were among infants weighing ≥2500 g. VLBW and LBW infants remained at an increased risk of dying with bronchiolitis after controlling for other risk factors. Other risk factors included increasing birth order, low 5-min Apgar score, young maternal age, unmarried mother and tobacco use during pregnancy. Conclusions. VLBW and LBW infants are at increased risk of dying with bronchiolitis, even when taking into account other risk factors. Although infants weighing <2500 g at birth are at increased risk for dying with bronchiolitis, the majority of bronchiolitis deaths occur among infants of normal birth weight.

Epidemiology of Invasive Haemophilus influenzae Type A Disease among Navajo and White Mountain Apache Children, 1988–2003

BACKGROUND Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of H. influenzae disease among Navajo and White Mountain Apache (WMA) children were among the highest reported worldwide. Routine Hib vaccination has significantly reduced rates of Hib disease in these populations. As Hib disease rates decrease to very low levels, there are concerns that non-type b strains of H. influenzae may emerge as more prevalent causes of invasive disease in children. METHODS We reviewed population-based, active laboratory surveillance data from the period of 1988-2003 for invasive H. influenzae type a (Hia) disease among Navajo and WMA children aged <5 years. Clinical information on cases was collected by chart review. A sample of Hia isolates from Navajo children was typed by pulsed-field gel electrophoresis (PFGE). RESULTS During 1988-2003, a total of 76 reported cases of invasive Hia disease occurred among Navajo and WMA children. The overall annual incidence was 20.2 cases per 100,000 population aged <5 years. There was no increase in Hia disease rates after Hib vaccination was introduced. The median age of patients was 12 months. Meningitis (50% of cases) was the most common presentation, followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis revealed a limited genetic diversity of Hia strains in this population. CONCLUSIONS Active surveillance data showed high rates of invasive Hia disease among Navajo and WMA children but no increase in the incidence after Hib vaccination was introduced. The presentation of Hia disease is similar to that of Hib disease in the prevaccine era.

Surveillance for meningococcal disease and strategies for use of conjugate meningococcal vaccines in the United States.

BACKGROUND Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate vaccines offer an opportunity for improved control of meningococcal disease. We evaluated the relative burdens of invasive meningococcal disease in US and examined the projected impact of various meningococcal conjugate vaccination strategies on rates of meningococcal disease. METHODS Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with meningococcal conjugate vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0-22-year-olds. RESULTS In models of serogroup C+Y meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine meningococcal conjugate vaccination, meningococcal disease could be reduced by 50% and deaths by 64%. CONCLUSIONS Use of meningococcal conjugate vaccine could markedly reduce meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.

Wresting SARS from Uncertainty

Organization (WHO) epidemiologist stationed in Vietnam, alerted the global health community to the high transmissibility and lethality associated with an apparently new respiratory disease. This disease, now called severe acute respiratory syndrome (SARS), is believed to have emerged in China in November 2002 and progressed to a global health threat by the spring of 2003 (1–3). On March 15, 2003, with clusters of SARS cases being reported from China, Hong Kong, Vietnam, Singapore, and Canada, WHO issued a global travel alert. At that point, the international health community faced a potential pandemic for which there were no identified causal agent, no diagnostic laboratory assays, no defined properties or risk factors for transmission, no infection-control practices of proven efficacy, and no known treatment or prevention measures. Given that setting, the declaration on July 5 that SARS had been contained (in less than 4 months after its initial recognition), represented a remarkable achievement for a truly extraordinary international public health effort. However, the SARS outbreak was not contained before it had had a substantial impact: 8,098 cases involving 774 deaths were attributed to SARS (4) (the original WHO case definitions [5] were revised during the outbreak to those shown in the Table); fear of contagion was rife in many communities, especially among healthcare workers; and billions of dollars had been lost in the airline and tourism industries, resulting in bankruptcies of airlines and other businesses. However, the SARS public health response effort was equally important: the world’s scientific, clinical, and public health communities had successfully instituted sensitive surveillance for the disease; isolation and infection-control practices—with intensive contact tracing and community containment, including quarantine—were effective in limiting continued spread in most cases; and the causative agent and diagnostic assays for detecting the disease were identified. Now, nearly 1 year after the world first faced this infectious disease challenge, the public health community is equipped with a broader understanding of the agent, its pathophysiology, clinical signs and symptoms, risk factors for transmission, and public health measures that can successfully contain the disease. The breadth of this understanding and international scope of the outbreak response are reflected in the range of manuscript topics in this issue Wresting SARS from Uncertainty

SARS and Pregnancy: A Case Report

We report a laboratory-confirmed case of severe acute respiratory syndrome (SARS) in a pregnant woman. Although the patient had respiratory failure, a healthy infant was subsequently delivered, and the mother is now well. There was no evidence of viral shedding at delivery. Antibodies to SARS virus were detected in cord blood and breast milk.

Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans

OBJECTIVE We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples. METHODS Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls. RESULTS TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR] = 0.7; P = .03 and OR = 0.9, P = .5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression. CONCLUSIONS TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.

SARS-associated Coronavirus Transmission, United States

To better assess the risk for transmission of the severe acute respiratory syndrome–associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Laboratory diagnosis of SARS-CoV infection is difficult; thus, sputum and stool specimens should be included in the diagnostic work-up for SARS-CoV infection.

Worldwide circulation of HSV-2 × HSV-1 recombinant strains

Homo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6–8 million years ago (MYA). Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes. Using over 150 genital swabs from North and South America and Africa, we detected recombinants worldwide. Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 × HSV-2 crossover followed by back-recombination to HSV-2. Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2. Our data add to previous in vitro and animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.