Rita F. Helfand

Zika Virus Disease in Colombia — Preliminary Report

Background Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. In October 2015, an outbreak of ZVD was declared after laboratory-confirmed disease was identified in nine patients. Methods Using the national population-based surveillance system, we assessed patients with clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results and pregnancy outcomes were evaluated for a subgroup of pregnant women. Concurrently, we investigated reports of microcephaly for evidence of congenital ZVD. Results By April 2, 2016, there were 65,726 cases of ZVD reported in Colombia, of which 2485 (4%) were confirmed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay. The overall reported incidence of ZVD among female patients was twice that in male patients. A total of 11,944 pregnant women with ZVD were reported in Colombia, with 1484 (12%) of these cases confirmed on RT-PCR assay. In a subgroup of 1850 pregnant women, more than 90% of women who were reportedly infected during the third trimester had given birth, and no infants with apparent abnormalities, including microcephaly, have been identified. A majority of the women who contracted ZVD in the first or second trimester were still pregnant at the time of this report. Among the cases of microcephaly investigated from January 2016 through April 2016, four patients had laboratory evidence of congenital ZVD; all were born to asymptomatic mothers who were not included in the ZVD surveillance system. Conclusions Preliminary surveillance data in Colombia suggest that maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus. However, the monitoring of the effect of ZVD on pregnant women in Colombia is ongoing. (Funded by Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

The challenges and strategies for laboratory diagnosis of measles in an international setting.

Serum-based measles-specific IgM EIAs are the recommended laboratory assays for diagnosis of acute measles infections and appear to be sufficient for measles control programs. However, serum samples are not ideal for molecular characterization of measles virus. Although neither laboratory nor field-based diagnostic tests that rival the EIAs have been developed, laboratory surveillance could be improved if specimen collection were simplified. Ideally the collection method should be noninvasive, have no requirement for a cold chain, and/or have no requirement for technically sophisticated equipment. Two alternative specimen collection technologies appear promising and can be used for both diagnostics and for collecting pertinent genotyping information: oral fluid and filter paper collection methods. These methods are compared along with their respective utilities in supporting measles diagnosis and strain surveillance.

Nonclassic measles infections in an immune population exposed to measles during a college bus trip

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3‐day bus trip using two buses. Questionnaires and serum samples were obtained 26–37 days after the trip. All participants had detectable measles‐neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM‐negative persons, those who rode on bus A with the index case‐patient had significantly higher microneutralization titers than those on bus B (P = .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles‐immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations. J. Med. Virol. 56:337–341, 1998.

Confirmation of Rubella within 4 Days of Rash Onset: Comparison of Rubella Virus RNA Detection in Oral Fluid with Immunoglobulin M Detection in Serum or Oral Fluid

ABSTRACT Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulin M (IgM) antibodies in serum, but approximately 50% of serum samples from rubella cases collected on the day of rash onset are negative for rubella virus-specific IgM. The ability to detect IgM in sera and oral fluids was compared with the ability to detect rubella virus RNA in oral fluids by reverse transcription-PCR (RT-PCR) by using paired samples taken within the first 4 days after rash onset from suspected rubella cases during an outbreak in Perú. Sera were tested for IgM by both indirect and capture enzyme immunoassays (EIAs), and oral fluids were tested for IgM by a capture EIA. Tests for IgM in serum were more sensitive for the confirmation of rubella than the test for IgM in oral fluid during the 4 days after rash onset. RT-PCR confirmed more suspected cases than serum IgM tests on days 1 and 2 after rash onset. The methods confirmed approximately the same number of cases on days 3 and 4 after rash onset. However, a few cases were detected by serum IgM tests but not by RT-PCR even on the day of rash onset. Nine RT-PCR-positive oral fluid specimens were shown to contain rubella virus sequences of genotype 1C. In summary, RT-PCR testing of oral fluid confirmed more rubella cases than IgM testing of either serum or oral fluid samples collected in the first 2 days after rash onset; the maximum number of confirmations of rubella cases was obtained by combining RT-PCR and serology testing.

Evaluation of the Immune Response to a 2-Dose Measles Vaccination Schedule Administered at 6 and 9 Months of Age to HIV-Infected and HIV-Uninfected Children in Malawi

BACKGROUND The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. METHODS Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. RESULTS Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. CONCLUSIONS An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).

Evaluating the impact of the HIV pandemic on measles control and elimination.

OBJECTIVE To estimate the impact of the HIV pandemic on vaccine-acquired population immunity to measles virus because high levels of population immunity are required to eliminate transmission of measles virus in large geographical areas, and HIV infection can reduce the efficacy of measles vaccination. METHODS A literature review was conducted to estimate key parameters relating to the potential impact of HIV infection on the epidemiology of measles in sub-Saharan Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV transmission rates and protective immune responses to measles vaccination. These parameter estimates were incorporated into a simple model, applicable to regions that have a high prevalence of HIV, to estimate the potential impact of HIV infection on population immunity against measles. FINDINGS The model suggests that the HIV pandemic should not introduce an insurmountable barrier to measles control and elimination, in part because higher rates of primary and secondary vaccine failure among HIV-infected children are counteracted by their high mortality rate. The HIV pandemic could result in a 2-3% increase in the proportion of the birth cohort susceptible to measles, and more frequent supplemental immunization activities (SIAs) may be necessary to control or eliminate measles. In the model the optimal interval between SIAs was most influenced by the coverage rate for routine measles vaccination. The absence of a second opportunity for vaccination resulted in the greatest increase in the number of susceptible children. CONCLUSION These results help explain the initial success of measles elimination efforts in southern Africa, where measles control has been achieved in a setting of high HIV prevalence.

Lack of Evidence of Measles Virus Shedding in People with Inapparent Measles Virus Infections

Serological evidence of measles virus infection has been detected among people exposed to measles who do not exhibit classical clinical symptoms. Throat swabs, lymphocytes, and serum and urine samples were collected from contacts of individuals with confirmed measles 12-16 days after exposure, during measles outbreaks occurring in 1998. Follow-up serum samples were drawn 2 weeks later. Samples were tested for measles IgM antibody by enzyme immunoassays and plaque reduction neutralization testing. Virus isolation and reverse transcriptase-polymerase chain reaction testing was attempted for all samples. None of the 133 contacts developed classical measles disease; 11 (8%) had serological evidence of infection. Duration of exposure of >or=3 h was the only significant risk factor for developing serological response (24% vs. 4% among contacts exposed for 1-2 h; relative risk, 6.0; 95% confidence interval, 1.9-19.2). None of the 133 contacts had virological evidence of infection by culture or polymerase chain reaction. We found no evidence that persons with inapparent measles virus infections shed measles virus.

Foundations of the severe acute respiratory syndrome preparedness AND response plan for healthcare facilities

OBJECTIVE To help facilities prepare for potential future cases of severe acute respiratory syndrome (SARS). DESIGN AND PARTICIPANTS The Centers for Disease Control and Prevention (CDC), assisted by members of professional societies representing public health, healthcare workers, and healthcare administrators, developed guidance to help facilities both prepare for and respond to cases of SARS. INTERVENTIONS The recommendations in the CDC document were based on some of the important lessons learned in healthcare settings around the world during the SARS outbreak of 2003, including that (1) a SARS outbreak requires a coordinated and dynamic response by multiple groups; (2) unrecognized cases of SARS-associated coronavirus are a significant source of transmission; (3) restricting access to the healthcare facility can minimize transmission; (4) airborne infection isolation is recommended, but facilities and equipment may not be available; and (5) staffing needs and support will pose a significant challenge. CONCLUSIONS Healthcare facilities were at the center of the SARS outbreak of 2003 and played a key role in controlling the epidemic. Recommendations in the CDCs SARS preparedness and response guidance for healthcare facilities will help facilities prepare for possible future outbreaks of SARS.

Combining Clinical and Epidemiologic Features for Early Recognition of SARS

Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.

Limited duration of vaccine poliovirus and other enterovirus excretion among human immunodeficiency virus infected children in Kenya

BackgroundImmunodeficient persons with persistent vaccine-related poliovirus infection may serve as a potential reservoir for reintroduction of polioviruses after wild poliovirus eradication, posing a risk of their further circulation in inadequately immunized populations.MethodsTo estimate the potential for vaccine-related poliovirus persistence among HIV-infected persons, we studied poliovirus excretion following vaccination among children at an orphanage in Kenya. For 12 months after national immunization days, we collected serial stool specimens from orphanage residents aged <5 years at enrollment and recorded their HIV status and demographic, clinical, immunological, and immunization data. To detect and characterize isolated polioviruses and non-polio enteroviruses (NPEV), we used viral culture, typing and intratypic differentiation of isolates by PCR, ELISA, and nucleic acid sequencing. Long-term persistence was defined as shedding for ≥ 6 months.ResultsTwenty-four children (15 HIV-infected, 9 HIV-uninfected) were enrolled, and 255 specimens (170 from HIV-infected, 85 from HIV-uninfected) were collected. All HIV-infected children had mildly or moderately symptomatic HIV-disease and moderate-to-severe immunosuppression. Fifteen participants shed vaccine-related polioviruses, and 22 shed NPEV at some point during the study period. Of 46 poliovirus-positive specimens, 31 were from HIV-infected, and 15 from HIV-uninfected children. No participant shed polioviruses for ≥ 6 months. Genomic sequencing of poliovirus isolates did not reveal any genetic evidence of long-term shedding. There was no long-term shedding of NPEV.ConclusionThe results indicate that mildly to moderately symptomatic HIV-infected children retain the ability to clear enteroviruses, including vaccine-related poliovirus. Larger studies are needed to confirm and generalize these findings.