OBJECTIVES: In Sindh Province, Pakistan, confirmed Crimean-Congo haemorrhagic fever (CCHF) increased from zero in 2008 to 16 in 2015-2016. To counter this increase, in 2016, we initiated structured CCHF surveillance to improve estimates of risk factors for CCHF in Sindh and to identify potential interventions. METHODS: Beginning in 2016, all referral hospitals in Sindh reported all CCHF cases to surveillance agents. We used laboratory-confirmed cases from CCHF surveillance from 2016 to 2020 to compute incidence rates and in a case-control study to quantify risk factors for CCHF. RESULTS: For the 5 years, CCHF incidence was 4.2 per million for the Sindh capital, Karachi, (68 cases) and 0.4 per million elsewhere. Each year, the onset of new cases peaked during the 13 days during and after the 3-day Eid-al-Adha festival, when Muslims sacrificed livestock, accounting for 38% of cases. In Karachi, livestock for Eid were purchased at a seasonal livestock market that concentrated up to 700,000 livestock. CCHF cases were most common (44%) among the general population that had visited livestock markets (odds ratio = 102). CONCLUSIONS: Urban CCHF in Sindh province is associated with the general public's exposure to livestock markets in addition to high-risk occupations.

Background: Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019. Aims: To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person.

When assessing multiple exposures in epidemiologic studies, epidemiologists often use multivariable regression models with main effects only to control for confounding. This method can mask the true effects of individual exposures, potentially leading to wrong conclusions. We revisited a simple, practical, and often overlooked approach to untangle effects of the exposures of interest, in which the combinations of all levels of the exposures of interest are recoded into a single, multicategory variable. One category, usually the absence of all exposures of interest, is selected as the common reference group (CRG). All other categories representing individual and joint exposures are then compared to the CRG using indicator variables in a regression model or in a 2×2 contingency table analysis. Using real data examples, we showed that using the CRG analysis results in estimates of individual and joint effects that are mutually comparable and free of each other's confounding effects, yielding a clear, accurate, intuitive, and simple summarization of epidemiologic study findings involving multiple exposures of interest.

Childhood lead exposure remains a key health concern for officials worldwide, contributing some 600,000 new cases of intellectually disabled children annually. Most children affected by high exposure to lead live in low- and middle-income countries. The leaded gasoline phase out in India was completed in 2000. Yet, in 2020, an estimated 275 million children aged 0 to 9 years had blood lead levels (BLLs) 5 g/dL known to adversely affect intelligence and behavior. Lead sources reported in India include spices, cookware, paint, traditional medicines and cosmetics, and lead-acid battery recycling and repair. However, their relative contribution has not been characterized. More than 200 lead pollution sites related to battery recycling and repair activities were identified in Bihar and Jharkhand, India. Ninety percent of the recycling sites had soil lead concentrations exceeding the US Environmental Protection Agency's standards. We compared blood and environmental lead levels in two groups of children in Patna, Bihar. Households in proximity to battery recycling operations (Proximal n = 67) versus households distal to these operations (Distal n = 68). The average age of children was 40 months; 46% were female. Overall, the geometric mean (GM) BLL was 11.6 g/dL. GM BLLs of children in Proximal and Distal households were not significantly different (10.2 g/dL vs. 13.1 g/dL respectively; p0.07). About 87% children, 56 Proximal and 62 Distal had BLLs 5 g/dl. Lead concentrations in environmental samples were significantly higher in Proximal households (soil mean 9.8 vs. 1.6 g/ft2; dust mean 52.9 vs. 29.9 g/ft2 p<0.001; Proximal vs. Distal respectively) whereas concentrations in all spices were higher in Distal households (mean 46.8 vs 134.5 ppm p<0.001; Proximal vs. Distal respectively), and turmeric (mean 59.4 vs. 216.9 ppm Proximal vs. Distal respectively). In multivariate analyses for all children lead in spices and turmeric and number of rooms in the house were significant while for the Proximal group only lead in spices remained in the model. The predictive value of these models was poor. For the Distal group, a model with lead concentration in spices, turmeric and soil and number of rooms in the house was a much better fit. Of the 34 water samples collected, 7 were above the Indian standard of 10 ppb for lead in drinking water (2 in the Proximal area, 5 in the Distal area). Children in Patna, Bihar, India are exposed to multiple sources of lead, with lead levels in house dust and loose, locally sourced spices the most likely to increase blood lead levels. A holistic approach to blood lead testing and source identification and remediation are necessary to prevent lead exposure.

BACKGROUND: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. METHODS: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. RESULTS: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). DISCUSSION: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

BACKGROUND: Field epidemiology training programs (FETPs) have trained field epidemiologists who strengthen global capacities for surveillance and response to public health threats. We describe how FETP residents and graduates have contributed to COVID-19 preparedness and response globally. METHODS: We conducted a cross-sectional survey of FETPs between March 13 and April 15, 2020 to understand how FETP residents or graduates were contributing to COVID-19 response activities. The survey tool was structured around the eight Pillars of the World Health Organization's (WHO) Strategic Preparedness and Response Plan for COVID-19. We used descriptive statistics to summarize quantitative results and content analysis for qualitative data. RESULTS: Among 88 invited programs, 65 (74%) responded and indicated that FETP residents and graduates have engaged in the COVID-19 response across all six WHO regions. Response efforts focused on country-level coordination (98%), surveillance, rapid response teams, case investigations (97%), activities at points of entry (92%), and risk communication and community engagement (82%). Descriptions of FETP contributions to COVID-19 preparedness and response are categorized into seven main themes: conducting epidemiological activities, managing logistics and coordination, leading risk communication efforts, providing guidance, supporting surveillance activities, training and developing the workforce, and holding leadership positions. CONCLUSIONS: Our findings demonstrate the value of FETPs in responding to public health threats like COVID-19. This program provides critical assistance to countries' COVID-19 response efforts but also enhances epidemiologic workforce capacity, public health emergency infrastructure and helps ensure global health security as prescribed in the WHO's International Health Regulations.

The World Health Organization monitoring and evaluation framework for the International Health Regulations (IHR, 2005) describes the targets for the Joint External Evaluation (JEE) indicators. For workforce development, the JEE defines the optimal target for attaining and complying with the IHR (2005) as 1 trained field epidemiologist (or equivalent) per 200,000 population. We explain the derivation and use of the current field epidemiology workforce development target and identify the limitations and lessons learned in applying it to various countries' public health systems. This article also proposes a way forward for improvements and implementation of this workforce development target.

Background: Childhood diarrhea deaths have declined more than 80% from 1980 to 2015, in spite of an increase in the number of children in low- and middle-income countries (LMIC). Possible drivers of this remarkable accomplishment can guide the further reduction of the half million annual child deaths from diarrhea that still occur. Methods: We used the Lives Saved Tool, which models effects on mortality due to changes in coverage of preventive or therapeutic interventions or risk factors, for 50 LMIC to determine the proximal drivers of the diarrhea mortality reduction. Results: Diarrhea treatment (oral rehydration solution [ORS], zinc, antibiotics for dysentery and management of persistent diarrhea) and use of rotavirus vaccine accounted for 49.7% of the diarrhea mortality reduction from 1980 to 2015. Improvements in nutrition (stunting, wasting, breastfeeding practices, vitamin A) accounted for 38.8% and improvements in water, sanitation and handwashing for 11.5%. The contribution of ORS was greater from 1980 to 2000 (58.0% of the reduction) than from 2000 to 2015 (30.7%); coverage of ORS increased from zero in 1980 to 29.5% in 2000 and more slowly to 44.1% by 2015. To eliminate the remaining childhood diarrhea deaths globally, all these interventions will be needed. Scaling up diarrhea treatment and rotavirus vaccine, to 90% coverage could reduce global child diarrhea mortality by 74.1% from 2015 levels by 2030. Adding improved nutrition could increase that to 89.1%. Finally, adding increased use of improved water sources, sanitation and handwashing could result in a 92.8% reduction from the 2015 level. Conclusions: Employing the interventions that have resulted in such a large reduction in diarrhea mortality in the last 35 years can virtually eliminate remaining childhood diarrhea deaths by 2030.

More than ever, competent field epidemiologists are needed worldwide. As known, new, and resurgent communicable diseases increase their global impact, the International Health Regulations and the Global Health Security Agenda call for sufficient field epidemiologic capacity in every country to rapidly detect, respond to, and contain public health emergencies, thereby ensuring global health security. To build this capacity, for >35 years the US Centers for Disease Control and Prevention has worked with countries around the globe to develop Field Epidemiology Training Programs (FETPs). FETP trainees conduct surveillance activities and outbreak investigations in service to ministry of health programs to prevent and control infectious diseases of global health importance such as polio, cholera, tuberculosis, HIV/AIDS, malaria, and emerging zoonotic infectious diseases. FETP graduates often rise to positions of leadership to direct such programs. By training competent epidemiologists to manage public health events locally and support public health systems nationally, health security is enhanced globally.

We commend Aakash Shrivastava and colleagues (April, 2017)1 on their meticulous epidemiological and toxicological investigation, which attributed severe encephalopathy in Indian children to methyl cyclopropyl glycine from lychees (also spelled litchis).1 | Lychees are widely cultivated and well renowned in China. Cautionary messages about the dangers of binging on lychees abound from ancient folklore to the modern electronic media, but these accounts are vague about the disease it causes. Accordingly, we searched the Chinese medical literature from 1960 to 2017, and identified 11 publications reporting 247 cases (11% fatal) of CNS disease that developed after eating lychees.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 The clinical and epidemiological features mirror the Indian experience. Children aged between 1 and 9 years accounted for 77% of cases. Patients had rapid onset (<1 h) of convulsions or unconsciousness, 85% between 0300 and 0900 h, and hypoglycaemia plus mild prodromal symptoms (table). All had eaten lychees within 24 h of disease onset, often in 300 g to 1 kg amounts for 2–10 consecutive days. All but one patient lived in lychee-producing, southern provinces.

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. MSM comprise roughly 2% of the US population, yet approximately two-thirds of new HIV infections are among MSM (Centers for Disease Control and Prevention, 2016). Additionally, significant racial and ethnic disparities exist with respect to HIV transmission among MSM. Based on the current HIV diagnoses rates in the US, about 1 in 2 African American men who have sex with men (AAMSM), 1 in 4 Latino MSM (LMSM) and 1 in 11 white MSM will be diagnosed with HIV during their lifetime (Center for Disease Control and Prevention (CDC), 2016a). In general, substance-using MSM are among the groups with the greatest risk for HIV infection (Centers for Disease Control and Prevention, 2011; Margolis, Joseph, Hirshfield, et al., 2014; Pines, Gorbach, Weiss, et al., 2014; Plankey, Ostrow, Stall, et al., 2007); nearly a third of incident HIV infections among MSM may be associated with non-injection drug use (Mansergh et al., 2008; Van Tieu & Koblin, 2009). Substance-using sexual minorities are more likely to underutilize substance use treatment (McCabe, Bostwick, Hughes, West, & Boyd, 2010) and may be an HIV transmission bridge to non-drug-using populations (Lambert et al., 2011). | With respect to alcohol use, high rates of both alcohol consumption and binge drinking have been documented among MSM populations (Finlayson et al., 2011). Additionally, previous studies have found associations between heavy drinking, as define as having 6 or more drinks on one occasion or 4 or more drinks daily, and HIV risk behaviors among MSM, such as condomless anal intercourse and greater number of sexual patterns (Colfax et al., 2004; Greenwood et al., 2001; Koblin et al., 2003a; Woolf & Maisto, 2009). Previous studies also suggest that many substance-using MSM populations engage in use of multiple substances, often concomitantly (Santos et al., 2013). There also may be a dose response with number and frequency of substances used with respect to condomless anal sex among HIV negative MSM (Santos et al., 2013). However, patterns of substance-use vary across racial and ethnic MSM populations, e.g. African American substance-using MSM being more likely to use crack/cocaine relative to other substance-using MSM populations (Goldstein, Burstyn, LeVasseur, & Welles, 2016; Halkitis & Jerome, 2008; Hatfield, Horvath, Jacoby, & Simon Rosser, 2009; Mimiaga, Reisner, Fontaine, et al., 2010; Paul, Boylan, Gregorich, Ayala, & Choi, 2014). Thus, it is important to better understand patterns of concomitant substance-use, e.g. methamphetamine, crack/cocaine and alcohol, across specific sociodemographic categories among MSM populations (Santos et al., 2013). Sociodemographic characteristics which may be particularly relevant for specific MSM populations include poverty and history of incarceration. For example, pronounced racial disparities have been found between AAMSM and other MSM populations with respect to structural barriers, such as low income, unemployment and incarceration, associated with HIV infection (Millet, Peterson, Flores, Hart, et al., 2012). Additionally, a recent study conducted by Rutledge et al, found a high proportion of MSM reporting both a history of incarceration and substance use. This study found rates of incarceration highest among men who classified themselves as “down-low”, e.g. endorsing secrecy about same-sex sexual behavior, promting the authors to posit that this population may engage in trading sex for money more often and thus increase their risk for incarceration (Rutledge, Jemmott, O'Leary, & Icard, 2016).

Previous observational studies have reported protective effects of hand-washing in reducing upper respiratory infections, little is known about the associations between hand-washing and good hygienic habits and seasonal influenza infection. We conducted a case-control study to test whether the risk of influenza transmission associated with self-reported hand-washing and unhealthy hygienic habits among residents in Fujian Province, southeastern China.Laboratory confirmed seasonal influenza cases were consecutively included in the study as case-patients (n = 100). For each case, we selected 1 control person matched for age and city of residence. Telephone interview was used to collect information on hand-washing and hygienic habits. The associations were analyzed using conditional logistic regression.Compared with the poorest hand-washing score of 0 to 3, odds ratios of influenza infection decreased progressively from 0.26 to 0.029 as hand-washing score increased from 4 to the maximum of 9 (P < 0.001). Compared with the poorest hygienic habit score of 0 to 2, odds ratios of influenza infection decreased from 0.10 to 0.015 with improving score of hygienic habits (P < 0.001). Independent protective factors against influenza infection included good hygienic habits, higher hand-washing score, providing soap or hand cleaner beside the hand-washing basin, and receiving influenza vaccine.Regular hand-washing and good hygienic habits were associated with a reduced risk of influenza infection. These findings support the general recommendation for nonpharmaceutical interventions against influenza.

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.

Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

BACKGROUND: Tungiasis is endemic in poverty-stricken communities of South and Central America, Africa, Asia, and the Caribbean. This ectoparasitosis, caused by the female sand flea Tunga penetrans, is associated with considerable longterm morbidity in severely affected patients, including toe deformation and limited mobility. In Haiti, tungiasis is poorly documented but is known to occur. This study is the first formal investigation of tungiasis in Haiti. METHODS: A total of 383 patients in four regions (Belle Fontaine, Vallue, Savanette, Cerca Carvajal) were examined and interviewed to determine disease prevalence, demographics and clinical presentation, and tungiasis-related behaviors. RESULTS: Prevalences of tungiasis ranged from 10.6 to 81.8% across the four regions. The overall prevalence of tungiasis in the patients examined was 31.1%. Of the affected patients, 63% were male and 37% were female, 37% were aged 0-10 years, and 100% reported pain and pruritus. Lesions occurred on the feet in 93.3% and on the hands in 22.7% of affected patients. The most common complications observed were chronic inflammation (54.2%) and hyperkeratosis (48.2%). CONCLUSIONS: This study establishes tungiasis as endemic in four regions of Haiti and reveals disease characteristics similar to those reported previously, suggesting that there are common factors underlying this disease in various regions, which are likely to be poverty-related. These findings emphasize the need to acknowledge tungiasis as a clinically relevant public health issue in order to decrease the frequency of tungiasis-related morbidity in endemic areas.

BACKGROUND: There has been a high mortality and morbidity rate of critical and fatal patients from hand, foot, and mouth disease in China in recent. Causes for development of critical and fatal disease remain unclear. METHODS: We performed a case-control study to assess the association between use of drugs and development of critical disease and death from hand, foot, and mouth disease. RESULTS: We found that glucocorticoids treatment was associated with a greater incidence of severe hand, foot, and mouth disease while andrographolides treatment was associated with a protective effect when they are used for treatment within 48 hours after onset or before being diagnosed as critical. CONCLUSIONS: We recommend that glucocorticoids should not be used for mild hand, foot, and mouth disease and andrographolides should undergo clinical trials for treatment of enterovirus 71 infections.

We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck.

BACKGROUND: Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy. METHODS: Three lots of methylprednisolone acetate were recalled by the pharmacy; examination of unopened vials later revealed fungus. Notification of all persons potentially exposed to implicated methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. We collected clinical data on standardized case-report forms, and we tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing. RESULTS: As of October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of December 10, there were 590 reported cases of infection in 19 states, with 37 deaths (6%). As of November 26, laboratory evidence of Exserohilum rostratum was present in specimens from 100 case patients (17%). Additional data were available for 386 case patients (65%); 300 of these patients (78%) had meningitis. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 16 to 92), and the median incubation period was 20 days (range, 0 to 120); 33 patients (9%) had a stroke. CONCLUSIONS: Analysis of preliminary data from a large multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.

BACKGROUND: Clusters of sudden unexplained death (SUD) in Yunnan Province, China, have been linked to eating Trogia venenata mushrooms. We evaluated the toxic effect of this mushroom on mice. METHODS: We prepared extracts of fresh T. venenata and Laccaria vinaceoavellanea mushrooms collected from the environs of a village that had SUD. We randomly allocated mice into treatment groups and administered mushroom extracts at doses ranging from 500 to 3500 mg/kg and water (control) via a gavage needle. We observed mice for mortality for 7 days after a 3500 mg/kg dose and for 24 hours after doses from 500 to 3000 mg/kg. We determined biochemical markers from serum two hours after a 2000 mg/kg dose. RESULTS: Ten mice fed T. venenata extract (3500 mg/kg) died by five hours whereas all control mice (L. vinaceoavellanea extract and water) survived the seven-day observation period. All mice died by five hours after exposure to single doses of T. venenata extract ranging from 1500 to 3000 mg/kg, while the four mice exposed to a 500 mg/kg dose all survived. Mice fed 2000 mg/kg of T. venenata extract developed profound hypoglycemia (median = 0.66 mmol/L) two hours after exposure. DISCUSSION: Hypoglycemia and death within hours of exposure, a pattern unique among mushroom toxicity, characterize T. venenata poisoning.

INTRODUCTION: Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006-2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms. METHODS: We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease. RESULTS: We identified 33 SUD, a 73% decline from 2002-2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata-exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test). DISCUSSION: Epidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue.

BACKGROUND: Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk. METHODS: We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment. RESULTS: Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables). CONCLUSIONS: Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.

INTRODUCTION: Between October 1 and December 10, 2006, Bao'an, China had a 5-fold increase in acute rotavirus gastroenteritis (ARGE) cases compared with the same time in 2005. To identify the risk factors for ARGE during this outbreak, we conducted a case-control study among children ≤24 months old from the most heavily affected area. METHODS: We defined an ARGE case as diarrhea, with group A rotavirus antigen detected from fecal samples by the enzyme-linked immunosorbent assay test. In the case-control study, 86 confirmed ARGE cases were identified. We enrolled 98 healthy control children matched by age. We administered questionnaires about exposures through telephone interviews. RESULTS: Of 8 general exposure types, we identified the following as being associated with ARGE: visiting outpatient services of hospital X, odds ratio (OR) = 7.1 (95% confidence interval [CI], 2.2-26); contact with other children with diarrhea, OR = 2.1 (95% CI, 1.1-3.7); and hand-washing before eating, OR = 0.48 (95% CI, 0.27-0.82). After improvements in the outpatient department of hospital X, ARGE incidence in the community during the ARGE transmission season (October through December) decreased from 4.3/10000 in 2006 to 1.4/10000 in 2009. CONCLUSIONS: Outpatient services in hospital X may have contributed to the transmission of ARGE and improvements in infection control practices in this setting were associated a marked decrease incidence of ARGE in this community.

BACKGROUND: Hygiene and social distancing are recommended control measures for hand, foot, and mouth disease (HFMD) and herpangina. However, empirical data to support this recommendation are limited. METHODS: During an outbreak of HFMD and herpangina due to infection by the human enterovirus 71, we defined a case as a vesicular papular rash on the hands, feet, buttocks, or oral mucosa and onset from April 30 to June 26, 2008. We selected 176 HFMD and herpangina case-children and a stratified random sample of 201 asymptomatic control-children; frequency matched according to residency status. We administered a questionnaire to the parents about their children's exposures and hygienic behaviors. RESULTS: Risk factors for HFMD and herpangina included playing with neighborhood children (odds ratio [OR]: 11 [95% confidence interval (CI): 6.2-17]), visiting an outpatient clinic for another reason ≤ 1 week before onset (OR: 20 [95% CI: 5.0-88]), and community exposures to crowded places (OR: 7.3 [95% CI: 4.1-13]). By using a score summarizing responses to 4 hand-washing questions, we found that 50% of the case-children and 2.5% of control-children had a poor score of 1 to 3, whereas 12% of the case-children and 78% of control-children had a good score of ≥7 (OR: 0.00069 [95% CI: 0.0022-0.022]) after we adjusted for residency, age, and community exposures by using logistic regression. CONCLUSIONS: Hand-washing by preschool-aged children and their caregivers had a significant protective effect against community-acquired HFMD and herpangina from the human enterovirus 71 infection.

PURPOSE: The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases. PATIENTS AND METHODS: We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot. RESULTS: All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, infinity; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 mug) in unused vials from implicated lots of methotrexate and cytarabine. CONCLUSION: Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.

BACKGROUND: Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown. METHODS: During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM ≥10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry. RESULTS: About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received. CONCLUSION: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.

BACKGROUND: We investigated an outbreak of gluteal abscesses following intramuscular (IM) injections given at a clinic in rural China to identify the causative agent, source, and method of exposure. METHODS: We defined a case as an abscess that appeared at the site of an injection given since June 1, 2006. We compared case rates by injection route, medication, and diluents. We reviewed injection practices, and cultured abscesses and environmental sites for mycobacteria. RESULTS: From October through December 2006, 5.8% (n=35) of 604 persons who had received injections at the clinic developed a case. All 35 cases occurred in 184 patients (attack rate=19.0%) who had received IM injections with various drugs that had been mixed with normal saline (NS); risk ratio=infinity; p<0.0001. No cases occurred in the absence of NS exposure. We identified Mycobacterium abscessus from eight abscesses and from the clinic water supply, and observed the inappropriate reuse of a 16-gauge needle left in the rubber septum of 100 ml multiple-dose bottles of NS in the clinic. Fourteen percent (n=527) of the 3887 registered residents of this village had been treated with IM drugs over a three-month period, often for minor illnesses. CONCLUSIONS: This outbreak of M. abscessus occurred from exposure to extrinsically contaminated NS through improper injection practices. Frequent treatment of minor illnesses with IM injections of antibiotics was likely an important contributing factor to the size of this outbreak.