Recently in Infectious diseases Category
The World Health Organization (WHO) now recommends a line-probe assay (LiPA) for the rapid, 2-day detection of multidrug-resistant tuberculosis* (MDR-TB), according to yesterday's press release. LiPA (eg, GenoType MTBDRplus; Hain LifeScience) extracts and amplifies sputum-derived Mycobacterium tuberculosis DNA, which is then hybridized with oligonucleotide probes to detect genes conferring rifampin or isoniazid resistance (eg, rpoB, katG, inhA).
In a 2006 study, the sensitivity and specificity of a rifampin-resistance LiPA (INNO-LiPA.Rif; Innogenetics) or traditional 2-3-month culture were examined in 420 new or retreatment sputum specimens from Asia, Africa, Europe, or Latin America (Studies suggest that rifampin resistance is a reasonable indicator of MDR-TB, where the prevalence of disease is high.) The concordance between LiPA and culture for rifampin resistance was 99.6%.
|
Result |
LiPA |
Culture |
|
Positive for M. tuberculosis DNA, % |
92.6 |
74.3 |
|
Positive for rifampin-resistance DNA, % |
30.6 |
30.8 |
|
Missed positive specimens |
22 |
100 |
WHO estimates that only 2% of the world's MDR-TB cases are recognized and treated appropriately, and that the multimillion-dollar initiative to systematically implement LiPA testing in 16 countries will increase that percentage to 15% or higher by 2012. Designated countries will receive the tests and appropriate training through the Stop TB Partnership's Global Drug Facility. According to WHO, Lesotho is ready to implement the use of LiPA for rapid MDR-TB detection, and Ethiopia will be ready by the end of this calendar year.
Photomicrograph of M. tuberculosis in sputum smear stained with Ziehl-Neelson acid-fast stain. Courtesy of CDC/Ronald W. Smithwick.
* Defined as resistance to both rifampin and isoniazid.
The onset of this year's rotavirus season was delayed by 2-4 months, and its magnitude was reduced by more than 50%, when compared with the previous 15 seasons of viral activity. These data coincide with the increasing use of the rotavirus vaccine (RotaTeq; Merck) in infants, according to an early release report from the MMWR. The live, oral vaccine was approved by the FDA in 2006, and its routine administration at 2, 4, and 6 months of age is recommended by the CDC's Advisory Committee on Immunization Practices.
Data from the National Respiratory and Enteric Virus Surveillance System (NREVSS) and the New Vaccine Surveillance Network* (NVSN) indicate that this year's rotavirus season began in late February, while the median onset of seasons during 1991-2006 occurred in mid-November (MMWR figure). Also the proportion of all positive rotavirus tests from mid-November 2007 to mid-April 2008 was substantially lower than the minimum number of positive tests during the previous 15 years.
Percentage of Positive Rotavirus Tests From NREVSS
(Data from 2008 are current through May 3)
*Data are from Monroe County, NY; Hamilton County, OH; and Davidson County, TN.
America's poor citizens, numbering approximately 36 million, are preferentially affected by more than a dozen ignored infections—including those caused by parasitic worms (left). A review of these "neglected infections of poverty" is provided by Peter Hotez, MD, PhD, in this month's issue of PLoS Neglected Tropical Diseases.
The cited diseases, many of which are endemic to third-world nations, are not confined to America's recent immigrants, writes Hotez, but prominently affect native-born people. He concludes that individuals in geographic regions of poverty—such as Appalachia, the Mississippi Delta, the Cotton Belt, the US-Mexican border, and Native American tribal lands—are particularly vulnerable. Although Hotez estimates high rates of these infections among the nation's poor (and specifically, among the minority poor), he emphasizes that an important obstacle to their control is the absence of recent and reliable prevalence data.
Soil-Transmitted Helminthic Infections
Toxocariasis: Up to 30% of rural African American children, mostly in the South, were seropositive for Toxocara canis, or dog roundworm, during the 1970s and 1980s, writes Hotez; however, disease surveys since that time are lacking. He estimates that 1.3-2.8 million Americans are exposed or infected, with at-risk populations in America's inner cities, the South, and Appalachia. In poor urban areas of the United States, playgrounds and sandboxes are often contaminated with T. canis eggs.
Strongyloidiasis: Threadworm, or Strongyloid stercoralis, may infect as many as 100,000 people in the United States, particularly in Appalachia. Hotez also reports that there is a 25% prevalence rate of strongyloidiasis (and a 75% rate of infection with the Schistosoma water fluke) among Somali and Sudanese immigrants. Consequently the CDC recommends presumptive treatment with antihelminthics in these groups.
Chagas disease: Infection with the flagellate protozoa Trypanosoma cruzi is traditionally an insect-borne illness, although the potentially fatal disease (for which there is no reliable treatment) may be transmitted through contaminated food and even by blood transfusion. Hotez cites the rise of domestic blood-sucking tratomines (or assassin bugs), which transmit the protozoa, and the 2007 report of human disease in post-Katrina New Orleans. Because of the high rate of infection among indigenous wildlife (eg, armadillos, opossums) in Louisiana and along the US-Mexican border, Hotez estimates the prevalence of Chagas disease in the United States at anywhere from 3000 to more than 1 million.
Amebiasis and leishmaniasis: Hotez reports that there are insufficient data to estimate the US prevalence of intestinal amebiasis, which is transmitted through food or water, and leishmaniasis, which is transmitted by the sand fly; however, he believes that poor populations along the US-Mexican border are especially at risk for these diseases. According to Wikipedia, US troops serving in the Middle East have experienced cutaneous leishmaniasis, or "Bagdad boil."
Bacterial Infections
Trench fever: Caused by gram-negative Bartonella quintana, trench fever (so-called because of its high prevalence among trench-living soldiers during World War I) is a louse-borne illness. Small outbreaks of trench fever have been documented among the homeless in Seattle and other urban areas since the 1990s; although the estimated US prevalence of the disease remains unknown.
Leptospirosis: A spirochetal infection of the urban poor, leptospirosis is transmitted through water contaminated by rat urine. Hotez reports that there are insufficient data to estimate the US prevalence of the infection, which can cause multisystem failure and DIC.
Viral Infections
Dengue fever: From 110,000 to 200,000 new cases of this mosquito-borne illness occur annually in the United States, clustering along the US-Mexican border. Candidate vaccines for dengue fever are in development.
Other poverty-level infections of concern include those caused by platyhelminths (cysticercosis, schistosomiasis, and echinococcus) and congentially transmitted diseases that preferentially affect poor American women (CMV, toxoplasmosis, syphilis). Although giardiasis is the most common parasitic infection in the United States, with an estimated prevalence of 2 million or more, Hotez writes that the disease does not appear to preferentially affect the poor.
He concludes, "Control of these neglected infections needs to be prioritzed...because it is both a highly cost-effective mechanism for lifting disadvantaged populations out of poverty and consistent with our shared American values of equity and equality."
Gross-out photo of mass of Ascaris lumbricoides worms, held by CDC's Henry Bishop, from the CDC/James Gathany.
An inactivated, whole-virus H5N1 vaccine is immunogenic and safe, according to a Baxter-sponsored, -designed, and -analyzed study. The results of the phase 1/2 trial were reported in this week's NEJM.
A total of 275 men or women received 2 doses of 1 of 6 randomly assigned versions of Baxter's vaccine, 21 days apart. The formulations of the vaccine, produced in Vero cells, contained various doses of hemagglutinin antigen, with or without alum adjuvant. The vaccine was produced from the wild-type strain A/Vietnam/1203/2004, which was originally cultivated from a 10-year-old Vietnamese boy who died of avian influenza in 2004 (Maines TR et al. J Virol. 2005;79:11788-11800.)
The vaccine induced direct neutralizing responses to A/Vietnam/1203/2004 (clade 1), as well as cross-neutralizing responses to strains A/Indonesia/05/2005 (clade 2) and A/Hong Kong/156/1997 (clade 3). The addition of adjuvant to the vaccine did not augment immunogenic responses; maximum responses were observed with nonadjuvant formulations containing either 7.5 or 15 µg of hemagglutinin. From 9% to 27% of enrollees experienced mild injection-site pain, and 6%-31% experienced headache.
The investigators proposed that whole-virus vaccine may be more immunogenic in unvaccinated groups than split- or partial-virus vaccines, and that the use of Vero cell culture (instead of embryonated chicken eggs) will reduce vaccine-production time during a pandemic.
The NEJM—perhaps sensitive to recent reports of medical ghostwriting and the use figurehead, academic authors for company-sponsored studies—provided the following information in the Methods section:
The manuscript was written by a subgroup of industry and academic authors; all authors contributed to the content, had full access to the data, and vouch for the completeness and accuracy of the data and data analysis.
The lead author of the study is Baxter's head of Global Research and Development, Hartmut J. Ehrlich, MD; the second author is Markus Muller, MD, of the Medical University of Vienna. According to the write-up, both physicians "contributed equally" to the article.
The development of an effective avian flu vaccine for humans is unlikely to happen too soon. CDC investigators recently discovered that North American strains of avian influenza A H7 have developed host-binding affinities that are similar to those of human influenza viruses. This property may facilitate human infection with avian influenza and human-to-human transmission.
A phase 3 study of Baxter's vaccine in Austria and Germany is active, but not yet recruiting subjects.
Colorized transmission electron micrograph of avian influenza A H5N1 virus (gold) grown in MDCK cells (green) from CDC/Cynthia Goldsmith.
In a cautionary, online slide show, the Multnomah County* Sheriff's Department warns of the cosmetic toll of meth addiction. Before-and-after mug shots show the result of drug-induced formication and the damaged caused by the victim's scratching and digging at skin, in an attempt to alleviate the creepy-crawly sensation.
Meth users with skin lesions may be especially prone to MRSA infection. Last year, investigators at the CDC and Georgia health departments reported an association between meth use and skin and soft-tissue infections (SSTI) due to MRSA in rural populations. Patients presenting to emergency or urgent-care facilities with MRSA SSTI were significantly more likely to have used meth within the last 3 months than control individuals (adjusted odds ratio, 5.10; 95% CI: 1.55, 16.79), and frequent skin picking was independently associated with MRSA SSTI (adjusted OR, 2.53; 95% CI: 1.22, 5.23).
MRSA: methicillin-resistant Staphylococcus aureus.
*Oregon.
Seven school-age children have contracted measles (rubeola) in DuPage County, IL, approximately 30 miles west of Chicago, according to the Illinois Department of Public Health. Investigation is pending, and the source of the infection remains unknown; however, inadequate immunization appears to be the cause of the outbreak.
In early May, the MMWR reported 64 cases of measles from January 1 to April 25 in the United States. A case of measles imported from Switzerland occurred April 17 in Chicago. As of May 23, the CDC has confirmed 103 US cases this year, the highest number for this time period since 2001.
Measles is spread by respiratory droplets or fomites, and infection occurs in 90% of those who are not vaccinated. The incubation period of the virus is 10-12 days, which is followed by mild-moderate fever, persistent cough, rhinitis, conjunctivitis, and pharyngitis. Approximately 3 days later, high fever, Koplik's spots (view image), and the characteristic skin rash (view image) appear. The measles rash—typically erythematous, blotchy, and slightly pruritic—begins on the face, hairline, and behind the ears and progresses to the chest, back, thighs, and feet. After approximately 2 weeks, the rash fades in reverse order.
Complications of measles include otitis (1/10), pneumonia, (1/15), encephalitis (1/1000), and thrombocytopenia. Pregnant women should avoid exposure to measles, owing to associated risks of miscarriage, premature labor, and low-birth-weight infants.
Measles cases are highly contagious, beginning 4 days before the rash appears and lasting until 4 days after the rash disappears. Vaccination confers approximately 98% immunity. The CDC recommends that all children should receive 2 doses of MMR vaccine (at 12-15 months and at 4-6 years). Adults without documented immunity should receive at least 1 MMR dose. International travelers should undergo age-dependent vaccination. Illinois reports an immunization coverage level among school-age children of 98%; however, the state does offer personal and religious exemptions.
Map of DuPage County from Wikipedia Commons.
Photos of Koplik's spots and measles rash from CDC.
Yesterday the Chinese Center for Disease Control and Prevention and the WHO Representative Office in China released their preliminary report on cases of hand, foot, and mouth disease (HFMD) due to enterovirus 71 (EV71) in the country. From January 1 to May 9 of this year, 61,459 cases and 36 deaths were reported on the mainland; the hardest-hit provinces have been Guangdong (11,374), Anhui* (9235), Zhejiang (6134), Shandong (4566), and Henan (3230). A report Wednesday from the Xinhua News Agency provides a current national HFMD death toll of 43. Also 2 children in Lhasa, Tibet, are believed to have contracted the disease.
The known death toll from China's May 12 earthquake is 51,151, according to Xinhua today; 288,431 are believed to be injured, and 29,328 remain missing.
*Home of Fuyang City.
Image of HFMD rash from the Report of the Hand, Foot, and Mouth Disease Outbreak in Fuyang City, Anhui Province and the Prevention and Control in China.
Hand, foot, and mouth disease due to enterovirus 71: deaths, 42; cases, 24,934.
Earthquake in Sichuan province: deaths, 14,866; estimated missing or buried, 40,000.
Map image highlighting earthquake epicenter in Sichuan province from Wikipedia.
In eastern China, 39 deaths due to hand, foot, and mouth disease (HFMD) are now reported by the official Xinhua News Agency, according to the AP. However, the disease, caused by enterovirus 71 (EV71), is "under control" in Fuyang City, writes Xinhua. There have been no deaths in the hard-hit metropolis of approximately 9 million people between May 2nd and 10th, and most hospitalized children who were in critical condition have recovered, reports a city official.
However, one of the recently reported HFMD deaths occurred in the eastern part of Anhui province, home of Fuyang City (which is in the northwestern part of the province). Another child died on the southern island province of Hainan, and 3 have died in the southern Guangdon province. The number of HFMD cases has escalated to 24,934 in 6 provinces, including Jilin in the far northeast. The cities of Beijing and Shanghai have also been affected.
2008 is becoming the year of reckoning, thanks in part to the anti-vax movement. Today's MMWR reveals that 64 cases of measles—a disease declared eliminated in the United States in 2000—have occurred so far this year in the country.* Compare that number with the average 62 cases annually during the last 8 years, and you've got the expectation for a dubious record in 2008.
According to the MMWR, most reported measles cases (84%) this year were due to imported disease from other countries (59 patients were US residents), and the overwhelming majority occurred in persons who were unvaccinated or whose vaccination status was unknown. Exactly half of the patients were younger than 5 years; 14 were younger than 1 year and therefore not eligible for immunization. Among the 21 US residents aged 16 months to 19 years, two thirds claimed exemption from vaccination because of religious or personal beliefs. Twenty-one measles patients were adults (including 1 US resident born before 1957).
Although 14 (22%) of those affected were hospitalized, there were no fatalities. Possibly the most shocking revelation is that 1 patient was an unvaccinated health care worker who acquired the disease in hospital. Another 17 individuals were infected while visiting a health care facility, including a 12-month-old child who, ironically, was exposed to the virus in the physician's office while receiving a routine MMR vaccine.
Details of the 2008 measles cases are tabulated below, and the MMWR provides a very nice annotated map:
|
Location |
No. Cases |
Date of Cases/ Outbreak |
Source |
|
|
11 |
01/25-02/16 |
|
|
|
3 |
02/05-02/25 |
|
|
|
22 |
02/07-04/20 |
|
|
Pima Co, AZ |
15 |
02/13-04/23 |
|
|
Missaukee Co, MI |
4 |
02/19-04/08 |
Unknown; genotype D5 (Index pt = unvaccinated 13-year-old) |
|
|
1 |
02/25 |
|
|
Milwaukee Co, WI |
4 |
03/19-04/09 |
|
|
|
1 |
03/23 |
Unknown |
|
|
1 |
04/12 |
Unknown |
|
Nassau Co, NY |
1 |
04/12 |
Unknown |
|
|
1 |
04/17 |
|
Although US vaccination levels are high, reports the MMWR, unvaccinated children tend to be clustered geographically or socially, which increases the risk of outbreaks. The article undermines the belief of some vaccine rejectionists that they can coast on the vaccine-provided immunity of other US residents. Cases to date show that the risk of imported disease remains high, and that unvaccinated individuals can propagate the spread of foreign-born infection. It is notable that a substantial measles outbreak occurred earlier this year in San Diego, CA, home of 3 vaccine-rejecting moms who were recently profiled by the NYT. The index patient in the San Diego outbreak was an unvaccinated child, who brought the infection back from Switzerland.
And California receives more negative attention today because of a pertussis outbreak that has closed a private school near San Francisco.
*Up until April 25.
