Dana L. Haberling

Rocky Mountain Spotted Fever in the United States, 2000–2007: Interpreting Contemporary Increases in Incidence

Rocky Mountain spotted fever (RMSF), a potentially fatal tick-borne infection caused by Rickettsia rickettsii, is considered a notifiable condition in the United States. During 2000 to 2007, the annual reported incidence of RMSF increased from 1.7 to 7 cases per million persons from 2000 to 2007, the highest rate ever recorded. American Indians had a significantly higher incidence than other race groups. Children 5-9 years of age appeared at highest risk for fatal outcome. Enzyme-linked immunosorbent assays became more widely available beginning in 2004 and were used to diagnose 38% of cases during 2005-2007. The proportion of cases classified as confirmed RMSF decreased from 15% in 2000 to 4% in 2007. Concomitantly, case fatality decreased from 2.2% to 0.3%. The decreasing proportion of confirmed cases and cases with fatal outcome suggests that changes in diagnostic and surveillance practices may be influencing the observed increase in reported incidence rates.

Infant and maternal risk factors for pertussis-related infant mortality in the United States, 1999 to 2004.

Background: Infants aged <12 months have the highest rates of complications and death from pertussis of any age group. Factors that increase the risk of pertussis-related death in infants are not well defined. Methods: The US Multiple Cause-of-Death and Linked Birth/Infant Death databases were used for 1999 to 2004 to examine pertussis-related infant mortality rates and to obtain anonymous records of infants with pertussis listed as a cause of death and of surviving infants. Infant and maternal characteristics present at the time of birth for infants who died with pertussis were compared with those of surviving infants. Results: During 1999 to 2004, 91 infant deaths were reported with pertussis as a cause of death. All infants were 7 months or younger; 58% were age <2 months. The average annual infant mortality rate attributed to pertussis was 3.8 (95% CI: 3.0–4.6) per 1,000,000 live births, and 13.1 (95% CI: 9.8–17.1) per 1,000,000 live births for infants aged <2 months. Infant pertussis deaths showed an independent association with birth weight <2500 g, female sex, Apgar score <8, and mother with <12 years education. The mortality rate among Hispanic infants aged <2 months was 2.6 times greater than among non-Hispanic infants of similar age. Conclusions: Ensuring pertussis booster vaccination of adults and adolescents in close contact with an infant is warranted to prevent transmission of pertussis to vulnerable infants, particularly infants too young to be immunized. Special emphasis should be given to women and infant settings in which the risk of infant pertussis death might be increased.

Risk Factors for Lower Respiratory Tract Infection Death Among Infants in the United States, 1999–2004

OBJECTIVE: To describe maternal and birth-related risk factors associated with lower respiratory tract infection (LRTI) deaths among infants. METHODS: Records for infants with LRTI as a cause of death were examined by using the linked birth/infant death database for 1999–2004. Singleton infants dying with LRTI and a random sample of surviving singleton infants were compared for selected characteristics. RESULTS: A total of 5420 LRTI-associated infant deaths were documented in the United States during 1999–2004, for an LRTI-associated infant mortality rate of 22.3 per 100000 live births. Rates varied according to race; the rate for American Indian/Alaska Native (AI/AN) infants was highest (53.2), followed by black (44.1), white (18.7), and Asian/Pacific Islander infants (12.3). Singleton infants with low birth weight (<2500 g) were at increased risk of dying with LRTI after controlling for other characteristics, especially black infants. Both AI/AN and black infants born with a birth weight of ≥2500 g were more likely to have died with LRTI than other infants of the same birth weight. Other risk factors associated with LRTI infant death included male gender, the third or more live birth, an Apgar score of <8, unmarried mother, mother with <12 years of education, mother <25 years of age, and mother using tobacco during pregnancy. CONCLUSIONS: Low birth weight was associated with markedly increased risk for LRTI-associated death among all of the racial groups. Among infants with a birth weight of ≥2500 g, AI/AN and black infants were at higher risk of LRTI-associated death, even after controlling for maternal and birth-related factors. Additional studies and strategies should focus on the prevention of maternal and birth-related risk factors for postneonatal LRTI and on identifying additional risk factors that contribute to elevated mortality among AI/AN and black infants.

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUND Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the countrys largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. INTERPRETATION Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING US Centers for Disease Control and Prevention.

Baseline estimates of diarrhea-associated mortality among United States children before rotavirus vaccine introduction.

Objectives: Deaths due to diarrhea among US children declined substantially from the 1960s through the 1980s, but have not been recently assessed. We examined diarrhea-associated mortality among young US children from 1992 to 2006 to establish baseline estimates through which the effect of rotavirus vaccines, introduced in 2006, can be assessed. Methods: National Center for Health Statistics multiple cause-of-death mortality data were used to examine diarrhea-associated deaths and death rates among US children 1 to 59 months of age during 1992–2006. The winter residual method was used to indirectly estimate the annual number of diarrhea-associated deaths attributable to rotavirus. Results: An average of 369 diarrhea-associated deaths/year (3320 total deaths) occurred among US children 1 to 59 months of age during 1992–1998 and 2005–2006. The diarrhea-associated death rate increased 40% between the first 3 and last 2 years of the study period, from an average of 1.6 deaths per 100,000 to 2.3 deaths per 100,000. Black children died at almost 4 times the rate of white children. Diarrhea-associated deaths showed a winter seasonal pattern similar to that of rotavirus, particularly among children 4 to 23 months of age. Using indirect methods, we estimated 25 yearly rotavirus-associated deaths during the study period. Rotavirus vaccination could potentially prevent 21 of these deaths annually. Conclusions: Diarrhea-associated mortality among US children stabilized but appears to be increasing in recent years. Rotavirus was associated with a small but significant number of preventable deaths. The national multiple cause-of-death data should prove useful for assessing mortality impact of rotavirus vaccination in the United States.

Pertussis-Associated Hospitalizations in American Indian and Alaska Native Infants

OBJECTIVE To investigate the burden of pertussis in American Indian and Alaska Native (AI/AN) infants. STUDY DESIGN AI/AN pertussis-associated hospitalizations between 1980 and 2004 were evaluated using Indian Health Service (IHS)/tribal inpatient data, which include all reported hospitalizations within the IHS/tribal health care system. RESULTS Between 1980 and 2004, 483 pertussis-associated hospitalizations in AI/AN infants were documented; 88% of cases involved infants age < 6 months. For this entire period, the average annual hospitalization rate was 132.7 per 100,000 AI/AN infants (95% confidence interval [CI] = 121.3 to 145.2), and 234.5 per 100,000 AI/AN infants age < 6 months (95% CI = 213.1 to 258.1). Between 2000 and 2004, the annual hospitalization rate was 100.5 per 100,000 AI/AN infants (95% CI = 81.6 to 123.7), which exceeds the estimated 2003 pertussis hospitalization rate of 67.7 per 100,000 in the general US infant population (95% CI = 61.9 to 73.5). The highest pertussis hospitalization rates in 2000 to 2004 were in AI/AN infants in the Alaska and Southwestern IHS regions of the United States. CONCLUSIONS The burden of pertussis in AI/AN infants is high, particularly so in infants age < 6 months in the Alaska and the Southwestern IHS regions of the United States. Ensuring implementation of vaccination strategies to reduce the incidence of pertussis in AI/AN, infants, adolescents, and adults alike is warranted to reduce the burden of pertussis in AI/AN infants.

Rickets and vitamin D deficiency in Alaska native children.

Abstract Background: Rickets and vitamin D deficiency appeared to increase in Alaskan children starting in the 1990s. We evaluated the epidemiology of rickets and vitamin D deficiency in Alaska native (AN) children in 2001–2010. Methods: We analyzed 2001–2010 visits with rickets or vitamin D deficiency diagnosis for AN and American Indian children and the general US population aged <10 years. We conducted a case-control study of AN rickets/vitamin D deficient cases and age- and region-matched controls. Results: In AN children, annual rickets-associated hospitalization rate (2.23/100,000 children/year) was higher than the general US rate (1.23; 95% CI 1.08–1.39). Rickets incidence increased with latitude. Rickets/vitamin D deficiency cases were more likely to have malnutrition (OR 38.1; 95% CI 4.9–294), had similar breast-feeding prevalence, and were less likely to have received vitamin D supplementation (OR 0.23; 95% CI 0.1–0.87) than controls. Conclusions: Our findings highlight the importance of latitude, malnutrition, and lack of vitamin D supplementation as risk factors for rickets.

Q Fever Is Underestimated in the United States: A Comparison of Fatal Q Fever Cases from Two National Reporting Systems

Two national surveillance systems capturing reports of fatal Q fever were compared with obtained estimates of Q fever underreporting in the United States using capture-recapture methods. During 2000-2011, a total of 33 unique fatal Q fever cases were reported through case report forms submitted to the Centers for Disease Control and Prevention and through U.S. death certificate data. A single case matched between both data sets, yielding an estimated 129 fatal cases (95% confidence interval [CI] = 62-1,250) during 2000-2011. Fatal cases of Q fever were underreported through case report forms by an estimated factor of 14 and through death certificates by an estimated factor of 5.2.

Impact of rotavirus vaccine on diarrhea-associated disease burden among American Indian and Alaska native children

OBJECTIVE: Beginning in 2006, the Indian Health Service (IHS) began rotavirus vaccination of American Indian and Alaska Native (AI/AN) infants. To assess vaccine impact, we examined trends in IHS diarrhea-associated hospitalization and outpatient visits among AI/AN children in the pre- and postrotavirus vaccine era. METHODS: Diarrhea-associated hospitalizations and outpatient visits among AI/AN children <5 years of age during 2001 through 2010 were examined by gender, age group, and region for prevaccine years 2001–2006 and postvaccine years 2008, 2009, and 2010. To account for secular declining trends observed in prevaccine years, expected diarrhea-associated hospitalization and outpatient rates for postvaccine years were generated by using Poisson regression analysis of the 2001–2006 annual rates. RESULTS: Coverage with at least 1 dose of rotavirus vaccine among AI/AN infants aged 3 to 5 months in the first half of 2008, 2009, and 2010 ranged from 48% to 80% in various IHS regions. The prevaccine average annual diarrhea-associated hospitalization rates among AI/AN children <5 years of age was 63 per 10 000 persons (range: 57–75 per 10 000), and declined to 39, 31, and 27 per 10 000 in 2008, 2009, and 2010, respectively. Observed 2008, 2009, and 2010 rates were 24%, 37%, and 44% lower than expected rates, respectively. Decreases in diarrhea-associated hospitalizations and outpatient visits were observed in all IHS regions. CONCLUSIONS: Diarrhea-associated hospitalization and outpatient visit rates among AI/AN children have declined after implementation of rotavirus vaccination in AI/AN populations.

Changing Trends in Viral Hepatitis- Associated Hospitalizations in the American Indian/Alaska Native Population, 1995-2007

Objective. We described the changing epidemiology of viral hepatitis among the American Indian/Alaska Native (AI/AN) population that uses Indian Health Service (IHS) health care. Methods. We used hospital discharge data from the IHS National Patient Information Reporting System to determine rates of hepatitis A-, B-, and C-associated hospitalization among AI/ANs using IHS health care from 1995–2007 and summary periods 1995–1997 and 2005–2007. Results. Hepatitis A-associated hospitalization rates among AI/AN people decreased from 4.9 per 100,000 population during 1995–1997 to 0.8 per 100,000 population during 2005–2007 (risk ratio [RR] = 0.2, 95% confidence interval [CI] 0.1, 0.2). While there was no significant change in the overall hepatitis B-associated hospitalization rate between time periods, the average annual rate in people aged 45–64 years increased by 109% (RR=2.1, 95% CI 1.4, 3.2). Between the two time periods, the hepatitis C-associated hospitalization rate rose from 13.0 to 55.0 per 100,000 population (RR=4.2, 95% CI 3.8, 4.7), an increase of 323%. The hepatitis C-associated hospitalization rate was highest among people aged 45–64 years, males, and those in the Alaska region. Conclusions. Hepatitis A has decreased to near-eradication levels among the AI/AN population using IHS health care. Hepatitis C-associated hospitalizations increased significantly; however, there was no significant change in hepatitis B-associated hospitalizations. Emphasis should be placed on continued universal childhood and adolescent hepatitis B vaccination and improved vaccination of high-risk adults. Prevention and education efforts should focus on decreasing hepatitis C risk behaviors and identifying people with hepatitis C infection so they may be referred for treatment.