Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease

A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015.

BACKGROUND: On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures. METHODS: We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples. RESULTS: From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (ORM-H = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (ORM-H = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination. CONCLUSION: Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas

How adequate is measles surveillance in the United States? Investigations of measles-like illness, 2010–2017

Given the availability of an effective and safe vaccine, the World Health Organization (WHO) declared that global measles eradication is achievable, and measles elimination goals have since been established as interim steps toward eradication. As part of a strategy to maintain elimination, the Pan American Health Organization (PAHO) and WHO stipulate a minimum annual reporting rate of discarded non-measles cases of ≥2 per 100,000 population, in order to ensure sensitive surveillance and adequate investigative effort. With its effective vaccination program, the United States in 2000 was among the first countries to verify elimination, although subsequently, it has not routinely reported discarded rates. We estimated MLI investigation rates among insured individuals during 2010–2017, using data from the MarketScan® databases. We defined “MLI investigations” as measles serologic testing within 5 days following diagnostic codes for measles-compatible symptoms and conditions. We provide a rationale for pre-specifying three subgroups for analysis: children aged ≤15 years; males aged 16–22 years excluding data from summer months; and males aged ≥23 years. MLI investigation rates ranged from 6.6─26.4 per 100,000, remaining stable over time except during the 2015 measles outbreaks when rates increased, particularly among young children. In addition to high vaccine uptake, measles elimination requires ongoing vigilance by clinicians and high-quality, case-based surveillance. Estimated rates of MLI investigations in this U.S. population suggesting that the quality of measles surveillance is sufficiently sensitive to detect endemic measles circulation if it were to be occurring

Impact of program transfer from a non-governmental organization to a district health office: Evaluation of a program integrating water treatment and hygiene kits into reproductive health and HIV services, Machinga District, Malawi, 2010-2012.

BackgroundIn September 2009, the Machinga Integrated Antenatal Water Hygiene Kit Program began addressing problems of unsafe water, high infant mortality, and low antenatal care (ANC) attendance in Machinga District, Malawi. In March 2011, the supporting international non-governmental organization transitioned management of the program to the Machinga District Health Office (DHO). We evaluated maternal and HIV service use before and after program transition to the DHO.MethodsWe compared pre- and post-transition periods by examining data recorded in ANC and maternal registries in 15 healthcare facilities (HCFs) by proportion z-tests. We classified HCFs by size, using the median monthly patient volumes as the split for large or small facilities. We used logistic regression to evaluate changes in the use of ANC, maternal, and HIV services and their interactions with HCF size.ResultsThe percentage of women attending their first ANC visit during the first trimester was similar in the pre-and post-transition periods (9.3% vs 10.2%). Although the percentage of women with ≥4 ANC visits was similar from pre- to post-transition (26.0% vs 24.8%), the odds increased among women in small facilities (OR: 1.37, 95% CI: 1.24-1.51), and decreased among women in large facilities (OR: 0.80, 95% CI: 0.75-0.85). Although a similar percentages of pregnant women were diagnosed with HIV in all HCFs in the pre- and post-transitions periods (6.4% vs 4.8%), a substantially larger proportion of women were not tested for HIV in large HCFs (OR: 6.34, 95% CI: 5.88-6.84). A larger proportion of women gave birth at both small (OR: 1.30, 95% CI: 1.16-1.45) and large HCFs (OR: 1.55, 95% CI: 1.43-1.67) in the post-transition vs. the pre-transition period.ConclusionsThe evaluation results suggest that many positive aspects of this donor-supported program continued following transition of program management from a non-governmental organization to a DHO

Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. Methods: We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Results: Of the 88 TIP cases identified during 2013–2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4–9 days after illness onset (ORadj = 2.2, 95%CI = 0.83–5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (ORadj = 11, 95%CI = 1.9–61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (ORadj = 9.0, 95%CI = 1.1–78). Conclusion: Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment