Results tagged “infectious diseases” from Pathophilia

A simplified table of the FDA-approved vaccines against the 2009 H1N1 virus is provided here, with a focus on age and dose recommendations. For complete data, see this week's MMWR.

The IM shots contain inactivated virus, and the nasal spray (from MedImmune) contains attenuated virus. Prefilled syringes do not contain mercury (that is, 25 microg Hg per 0.5 mL of vaccine, in the form of thimerosal preservative). When 2 doses are recommended, they are administered approximately 4 weeks apart.

The nasal spray vaccine is indicated for healthy, nonpregnant persons aged 2-49 years and should not be administered to persons with asthma. The dose of the nasal spray is divided equally between each nostril.  

Note: These data are for informational purposes only and should be confirmed by referring to authoritative sources (eg, the CDC) and/or a treating healthcare professional.

* Latter approved by FDA for age group on 11/12/09.

Pneumococcal vaccines, which can protect against influenza complications, are underused. And there is no shortage of these vaccines. These facts were relayed by Thomas Frieden in today's CDC press conference.

The CDC recommends the PCV7 vaccine (Prevnar; Wyeth) routinely for children younger than 2 years of age (1 dose each at 2, 4, 6, and 12-15 months) and older children who have not completed the 4-series vaccination.

The CDC recommends the PPSV23 vaccine (PneumoVax; Merck) for all adults aged 65 years or older and any individual 2-64 years of age with a long-term health problem (eg, diabetes) or a condition that lowers resistance to infection (including therapy). The CDC also recommends the PPSV23 vaccine for adults 19-64 years of age who smoke or have asthma.

Pneumococcal immunization protects against infection with Streptococcus pneumoniae, the most common bacterial pathogen in reported fatal cases of H1N1 infection to date.

For authoritative and comprehensive information on this subject, see the CDC web site.

PCV7 = 7-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

Photomicrograph of S. pneumoniae grown from blood culture from the CDC/Dr. Mike Miller.

According to today's MMWR.

Among the 77 fatal cases of 2009 H1N1 influenza that were reported in the United States from May 1 to August 20, bacterial pathogens were identified in 22 cases (29%). Streptococcus pneumoniae was detected in 10 (45%).

The breakdown:

And no state remains unaffected.

The CDC advises, however, that heightened H1N1 activity does not reflect the severity of disease. At least 99% of all subtyped influenza virus samples (n = 1402) are the 2009 H1N1 virus.

Also according to CDC data, the in-hospital death ratio associated with influenza-like illness (ILI), as of September 19, was 0.093 (mortality rate, 9.3%). US deaths include 49 children.

Multiplying the US hospitalization ratio for April 15 to July 24 (0.114) by the CDC's latest in-hospital death ratio for ILI provides a case-fatality ratio of 0.0106 (mortality rate, ~1%). However, a Harvard epidemiologist recently estimated the H1N1 death rate to be considerably lower—from 0.007% to 0.045%.

Vaccines for the 2009 H1N1 virus are expected to be available next month (that is, in a few days), with the nasal-spray vaccine preceding the shot vaccine in the US marketplace. Candidates for the nasal vaccine are nonpregnant persons 2-49 years of age.

Newly released results from a national survey (N = 1678), performed by the University of Michigan in August, revealed that a minority of parents plan to have their children vaccinated against the pandemic H1N1 virus. (The CDC currently recommends that all individuals from 6 months to 24 years of age undergo H1N1 [swine flu] vaccination.) Surveyed parents reported that they are more likely to have their children receive the seasonal influenza vaccination.

Parents' perception of the risks associated with H1N1 flu were closely linked to the likelihood of opting for the vaccine. Notably Hispanic parents were more likely to report their intention of having their children undergo vaccination—possibly because they perceive a higher threat from the disease than non-Hispanic parents. For instance, Hispanic parents may be more aware of the recent history of H1N1 disease in Mexico.

That's because...

The injected vaccine for seasonal influenza was more effective at inducing immunity than the nasal-spray version in adults, according to a study published yesterday in the NEJM. The results can possibly be applied to vaccine options for pandemic H1N1. (But then again, maybe not. Read on.)

In a randomized, double-blind, placebo-controlled study of 1952 healthy adults (18-49 years of age) during the 2007-2008 influenza season,* the injected vaccine (which contains inactivated virus) reduced the relative risk of laboratory-confirmed influenza by 50%, when compared with the nasal-spray vaccine (which contains live, attenuated virus). The rates of absolute efficacy against influenza A (predominately the H3N2 virus) were 72% and 29% for the shot and spray vaccines, respectively.

Other data indicate, however, that the spray vaccine is more effective for the prevention of flu than the injection in young, vaccine-naive children (2 doses) and in older children (1 dose).

It is speculated that the nasal-spray vaccine is relatively less effective in adults, because preexisting seasonal flu antibodies thwart the vaccine antigens at their entry point in the nasal passages. But because the pandemic H1N1 virus is new to everybody, the nasal-spray vaccine may work comparably in children and adults.

* According to the CDC, circulating viruses during this season in the United States were influenza A (71%) and influenza B (29%). Early in the season, influenza A H1N1 viruses predominated, followed by an increase in circulating H3N2 viruses. Influenza B viruses were more common during the tail of the season. Circulating H3N2 viruses were most common overall.

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And on a related note...

A high-profile anecdote of confirmed illness with the pandemic H1N1 virus was provided yesterday by CNN's Sanjay Gupta. Gupta's prominent symptoms were similar to those of seasonal flu: a hacking cough, fever, nausea, and body aches. Although Gupta reported, "[T]his was the sickest I have ever been," he recuperated after a couple of days of symptomatic treatment and bed rest. He evidently did not receive antiviral therapy (eg, oseltamivir [Tamiflu]).

Seasonal Influenza Vaccine (available now)

Who should receive the seasonal influenza vaccine?

• Individuals from 6 months to 19 years of age and individuals 50 years of age or older
• Pregnant women
• Persons with certain chronic medical conditions
• Individuals living in nursing-home or long-term care facilities
• Persons living or working with others who are at risk for influenza-related complications (eg, healthcare workers, daycare employees).

Who is a candidate for the intranasal spray vaccine, which contains 3 live, attenuated seasonal influenza viruses?

Healthy, nonpregnant persons 2-49 years of age.

Who is a candidate for the intramuscular vaccine, which contains 3 inactivated seasonal influenza viruses?

Children 6-35 months of age (dose, 0.25 mL) and individuals 3 years of age or older (dose, 0.5 mL).

Who should receive 2 doses of the seasonal influenza vaccine (each separated by 4 weeks)?

Children younger than 9 years of age who 1) are receiving the seasonal influenza vaccine for the first time or 2) received the vaccine for the first time during the previous influenza season and received only 1 dose.

Pandemic H1N1 (Swine Flu) Vaccine (expected in October)

Who should receive the swine flu vaccine?

• Pregnant women
• Persons who live with or care for infants younger than 6 months of age
• Healthcare and emergency medical personnel
• Persons aged from 6 months to 24 years
• Individuals aged 25-64 years who are at risk for influenza-related complications (eg, persons with asthma, diabetes, hypertension, HIV). 

Who is a candidate for the intranasal spray vaccine, which contains the live, attenuated pandemic H1N1 virus?

The same individuals who are candidates for the intranasal seasonal influenza vaccine: healthy, nonpregnant persons 2-49 years of age.

Who is a candidate for the intramuscular vaccine, which contains the inactivated pandemic H1N1 virus?

All individuals who are priority candidates for the pandemic H1N1 vaccine.*

Who should receive 2 doses of the swine flu vaccine (each separated by 3-4 weeks)?

Late-breaking data suggest that 1 vaccine dose will be sufficient to induce a protective immune response in persons 10 years of age or older. Children from 6 months to 9 years of age, however, will likely require 2 doses of vaccine.

* I suspect that doses, like those for the seasonal influenza vaccine, are cut by half for children 6-35 months of age; however, I have not yet confirmed this information.

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The US Department of Health and Human Services (HHS) recently ordered 56 million more doses of the pandemic H1N1 vaccine from MedImmune and sanofi pasteur for an additional $438,143,025. The total US government spend on the pandemic H1N1 vaccine is now $2,255,120,945, which amounts to $8.98 per vaccine dose.

• Estimated, cumulative number of pandemic H1N1 infections in the United States between April and June: more than 1 million. (See yesterday's post, for example, for how the estimated case number affects the estimated mortality rate.)
• Peaks of activity: May and June nationwide; late August in the Southeast.
• Confirmed H1N1 hospitalization rate from April to August: generally lower than that for seasonal influenza but higher than usual for the time period.
• In-hospital death rate from mid-April to August 30th: 6.5% (593/9079); proportion of deaths due to pneumonia and influenza "within the bounds" of summertime expectations.
• Circulating virus: 97% pandemic H1N1 that is sensitive to antiviral treatment.
• Antiviral drug sensitivity: 99.4% of 1372 tested samples are susceptible to oseltamivir (Tamiflu; Roche); oseltamivir-resistant viruses still susceptible to zanamivir (Relenza; GSK); all viruses resistant to amantadine and rimantadine.
• Recommendations for persons with influenza-like illness (ILI): after afebrile (untreated), stay home for another 24 hours.
• Antiviral treatment recommendations: early therapy for persons with severe ILI and those individuals with suspected ILI and risk factors for complications (<5 years of age; >64 years of age; or underlying health conditions, including pregnancy).
• Vaccines for seasonal influenza: available now and urged for all children, persons 50 years of age or older, and those at greater risk for influenza-related complications.
• Vaccines for pandemic H1N1: still expected by mid-October; first in line have already been designated by the CDC.

Depiction of H1N1 virus from Wikipedia.

Lipsitch proposes that the mortality risk due to the 2009 H1N1 virus is comparable to that of a "moderate" influenza season—less than 0.1%.** The epidemiologist bases his calculation on reports of influenza-like illness throughout the world, as well as reports of hospitalizations and confirmed deaths.

Working backward, one can conclude that Lipsitch estimates the number of people infected so far with the 2009 H1N1 virus worldwide at several million.

* Calculated by multiplying the US hospitalization ratio from April 15 to July 24, or 0.114, by a recent in-hospital death ratio (eg, 0.065) and then multiplying by 100.

** Although CDC data suggest a death rate for seasonal flu that is higher than 0.045%. According to the Centers, 5%-20% of the US population is affected each year by seasonal influenza. The US population is approximately 300 million, so that means 15-60 million are infected annually. About 36,000 people die of seasonal flu, for an annual mortality rate of 0.06%-0.24%. About 200,000 are hospitalized, for a hospitalization rate of 0.3%-1.3%.

Depiction of H1N1 virus from Wikipedia.

Last week's late-breaking data indicated that 1 vaccine dose (15 micrograms), instead of the originally anticipated 2, will be sufficient to induce a "robust" immune response in most adult recipients. The optimal dose in children, however, has not been confirmed.

The vaccines are produced by using the same methods as those for seasonal flu vaccines, including viral cultivation in chicken eggs. (WHO nicely explains the vaccine-manufacturing process here.) Consequently people with "severe or life-threatening" allergies to chicken eggs should not receive the vaccine. Vaccines will also be available in preserved (ie, thimerosal containing) and nonpreserved formulations.

Side effects of the injected and nasal-mist vaccines are anticipated to be similar to those seen with the seasonal flu vaccines.

Five companies contracted with the US Department of Health and Human Services (HHS) to create and manufacture a vaccine against the novel H1N1 virus; only GlaxoSmithKline failed to receive vaccine approval yesterday. Reasons for the delayed or deferred approval of GSK's vaccine were not provided by the FDA or the company.

According to a cached version of the web page detailing HHS's contracting activities, the following government orders for novel H1N1 vaccines were made in May and June.

HHS = Health and Human Services.

Addendum: An updated HHS web page reveals that MedImmune received a total of $151,008,000 in contracts for May and June. The cumulative government spend is therefore $1,815,977,920. With an order of 195 million doses, that's $9.31 per vaccine dose.  

The latest WHO update (August 30th) for infections with the novel H1N1 virus indicates more than 254,206 cases globally and at least 2837 deaths, for a crude mortality rate of 1.1%. However, this mortality rate is likely overestimated, because the total number of H1N1 cases is underestimated. Pitfalls in calculating the death rate (or the case-fatality ratio) during the H1N1 pandemic are discussed here.

Dr. Thomas Frieden of the Centers for Disease Control and Prevention (CDC) conducted this week's broadcasted press conference on the status of the novel H1N1 epidemic in the United States.

Points made.

• The bad news: Novel H1N1 virus is here and spreading, and notably, infection didn't abate during the summer ("very usual"). Expect to see more cases in the coming months.
• The good news: The virus has not mutated, as yet, to become more deadly; and so far, antiviral-resistant strains of H1N1 have not been observed. (See Addendum.)
• The caution: But influenza is unpredictable, and readiness for the worst is imperative.
• The verified data:
  a) There have been 36 pediatric deaths in the United States, details of which are in the latest issue of the MMWR; children with special needs appear to be particularly vulnerable to infectious complications, including death.
  b) Recent experience in the Southern Hemisphere (5 countries) is similar to that in the United States (during the Spring); there have been hospitalization challenges but no increase in the H1N1-related death rate.
  c) The Institute of Medicine (IOM) issued a report today recommending fitted N95 respirators, instead of the typical face mask, for healthcare workers who interact with H1N1-infected patients.*
• The unverified data: A 1-dose vaccine, which was recently approved in China.
• The 2-dose vaccine:
  a) Still expected in mid-October.
  b) To induce effective immunity, 2 doses are anticipated to be necessary.
  c) Recommended groups for vaccination remain the same.
  d) The vaccine itself is free, although administration may not be; the government is in the process of releasing $1.5 billion to enable/facilitate vaccine administration.
  e) Vaccination programs will be run on the local level (eg, state). 
• The upcoming surveillance: For possible adverse events (eg, Guillain-Barre syndrome, miscarriages) associated with vaccination.
• The challenge to safeguard healthcare resources:
  a) Most cases of novel H1N1 infection are mild and don't necessitate laboratory testing or antiviral treatment.
  b) Stay home if you're sick.
  c) Cover your face when coughing or sneezing.
  d) Wash your hands.
  e) Don't go to the doctor unless you're severely ill or have an underlying condition (although it's important to be seen promptly in these cases, so that antiviral therapy can be instituted in a timely fashion [ie, within 48 hours of symptom onset]).
  f) To employers: Don't require a permission note from an employee's doctor before the employee can return to work; in general, telecommuting may be a good idea.

* The IOM was not charged with considering cost, when making its recommendation.

Depiction of H1N1 virus from Wikipedia.

09/05/09 addendum: In its August 12th report, WHO indicated knowledge of 12 cases of disease that is resistant to oseltamivir (Tamiflu; Roche). The mutated virus, however, remains sensitive to zanamivir (Relenza; GSK). Oseltamivir-resistant cases occurred sporadically throughout the world and were apparently not connected. 

The latest WHO update for infection with the novel H1N1 virus indicates more than 209,438 cases of disease globally and at least 2185 deaths, for a crude mortality rate of 1%. However, this mortality rate is likely an overestimate of the actual H1N1-related mortality rate. Pitfalls in calculating the death rate (or the case-fatality ratio) during the H1N1 pandemic are discussed here.

Data from April 24 to July 25 indicate the following overall attack and hospitalization rates (per 100,000) by age group within the city's 77 communities.

Consequently the overall attack rate among children aged 5-14 years is more than 14 times that among adults aged 60 years or older. Hospitalization rates are also considerably higher among the younger pediatric populations. These data support current guidelines for preferentially vaccinating younger age groups against the novel H1N1 virus.

Reasons for the higher attack and hospitalization rates among children may be related to the existence of partial (ie, cross-reactive) immunity to the novel H1N1 virus among the elderly and/or higher virus-transmission/contact rates among children.

Overall attack and hospitalization rates are also higher among minority ethnic groups, for unclear reasons; although the relatively higher prevalence of underlying conditions, like asthma or diabetes, in minority ethnic groups may explain their increased vulnerability to H1N1 infection.

Among those hospitalized, 40 (19.5%) were admitted to an intensive-care unit; 9 (4%) required mechanical ventilation. The rates of preexisting asthma and diabetes in hospitalized patients were 21% and 7%, respectively. Also notable is the fact that 14 (7%) hospitalized patients were pregnant. Among those surviving patients with admission and discharge data (n = 97), the median hospital stay was 2 days (range, 1-11 days).

As of August 24, there were 7 H1N1-related deaths in Chicago (crude mortality rate, 0.45%); all were associated with respiratory compromise.

1. 20-year-old pregnant woman
2. 54-year-old women with acute myeloid leukemia
3. 22-year-old man receiving long-term hemodialysis
4. 32-year-old obese* man with asthma
5. 52-year-old man with lymphoma
6. 26-year-old woman with no reported chronic health conditions
7. 47-year-old woman with no reported chronic health conditions

The CDC editors note that the true hospitalization rate and, particularly, the attack rate associated with the novel H1N1 virus in Chicago might be overestimated, because the number of confirmed cases is underestimated. To alleviate laboratory workloads, H1N1 testing was discouraged for outpatients by the city's Department of Public Health after April 30th.

The most common clinical symptoms among affected Chicagoans are fever (73%), cough (68%), sore throat (29%), and dyspnea (15%).

* Another recent MMWR report from the Michigan Department of Community Health suggests that obese and extremely obese patients may be particularly vulnerable to complications associated with novel H1N1 infection.

Although the crude mortality rate for infection with the novel H1N1 virus has been supplied at this blog (by using raw data from the World Health Organization), there are a number of pitfalls when calculating this value during an epidemic/pandemic. The drawbacks of using the simple equation for the mortality rate—that is, dividing the number of known deaths (the numerator) by the number of known cases (the denominator)*—are outlined in a recent (if somewhat mathematically challenging) article in the BMJ.

Briefly, however, the UK authors highlight 2 general sources of potential error: 1) difficulties with case ascertainment; and 2) inevitable delays between infection onset, death, and subsequent reporting.

Case Ascertainment

Particularly as the pandemic advances (for example, in the hot zones of Mexico and the United States), there is the likelihood of underrecognizing (or simply ignoring) mild cases of infection. Consequently the denominator is underestimated, and the mortality rate is overestimated.

But deaths due to H1N1 may also be unrecognized. For instance, some vascular deaths may not be recognized as caused by influenza. Also, at least in developing areas, hospital surveillance may be poor. Consequently the numerator and the mortality rate are underestimated.

The authors' solution (at least for the underrecognition of cases) is to use closely monitored hospitalization data from the early part of the pandemic and in-hospital mortality data later in the pandemic (when total case ascertainment becomes difficult). The overall mortality rate (or really, the case-fatality ratio) is the hospitalization ratio X the fatality ratio among hospitalized cases.

Of course, this calculation requires sufficient sample sizes. For instance, to obtain 95% confidence intervals for a case-fatality ratio ranging from 0.5 to 1.5, you would need ~1100 cases and ~200 hospitalizations. An important assumption with this solution, the authors stress, is that the hospitalization ratio and the in-hospital death ratio remain constant over the course of the pandemic; but guidelines for the hospitalization of H1N1 cases, in particular, may change as the pandemic advances.

Nevertheless, by using numbers from the CDC, the H1N1 case-fatality ratio can be estimated according to the authors' equation. There were 43,771 confirmed or probable cases of novel H1N1 infection in the United States from April 15 to July 24,** resulting in 5011 hospitalizations. Therefore the hospitalization ratio for this time period was 0.114. As of August 20, there have been 522 deaths among 7982 hospitalizations, for an in-hospital death ratio of 0.65 0.065. The case-fatality ratio in the United States is therefore 0.114 X 0.65 0.065, or 0.0075 (and the mortality rate is 0.75%).

Inevitable Delays

The case-fatality ratio may also be underestimated when there is a delay between the onset of infection and knowledge of the final outcome of the case. This effect, the authors note, is known statistically as censoring—which subsides after the pandemic peaks.

The authors' solution is to divide the number of deaths by the number of cases in which the outcome is known; however, this solution may be problematic when there is a relatively long delay between symptom onset and death, as is typical in cases of influenza.

Their second proposed solution is an estimator, which contains a big, fat sigma (a sigma!), to calculate the case-fatality ratio on a particular day. The estimator also requires knowledge of the time from symptom onset to death to approximate the expected number of deaths on the particular day in question.

The estimator is reproduced here for statisticians, epidemiologists, and the otherwise fanatical. Knock yer-selves out (and feel free to post yer calculation).

1. pregnant women;
2. persons who live with or provide care for infants younger than 6 months of age;
3. healthcare and emergency medical services personnel;
4. individuals from 6 months to 24 years of age; and
5. individuals 25-64 years of age who have medical conditions (eg, asthma, hypertension, diabetes, HIV) that increase the risk of influenza-related complications.

This population, in total, is estimated to include 159 million Americans, although the estimate does not account for overlap among subgroups (eg, a physician-parent with a young infant). The CDC advises that vaccination of these subgroups should begin as soon as vaccine is available.

The CDC has also identified sub(sub)groups of candidates, should the vaccine supply not meet the targeted demand:

1. pregnant women;
2. persons who live with or provide care for infants younger than 6 months of age;
3. healthcare and emergency medical services personnel who have direct contact with patients or infectious material;
4. children from 6 months to 4 years of age; and
5. children and adolescents 5-18 years of age who have medical conditions that increase the risk of influenza-related complications.

Licensed vaccines, which are expected to be available in the United States by mid-October, are necessary because the vaccines for seasonal influenza are not likely to provide adequate protection against the novel H1N1 virus.

As of today, the World Health Organization reports 1799 deaths due to the novel H1N1 swine-flu virus among a global total of more than 182,166 cases. By using these numbers, the overall mortality rate is 0.98% (although the actual rate is somewhat lower). The death rate as of August 6th was 0.82%. Again most of the deaths (~87%) have occurred in the Americas.

News of the newly available, When Zombies Attack!: Mathematical Modelling of an Outbreak of Zombie Infection, by 4 Canadian mathematicians. Their mothers, despite the authors' statistically probable dateless existences,* must be so proud. The web server for the University of Ottawa math department is inundated, just like the Winchester pub in Shaun of the Dead!

For the mathematically unsophisticated, the bulk of the paper is a blur of italicized English or Greek letters and a few arabic numbers, organized by the obligatory parens, brackets, and braces. The occasional chart and what look like electrical diagrams (really model flow diagrams) make the paper unreadable to the ignorant. At least, until the amusing Discussion section.

Making a half-hearted nod to similarities between a zombie attack and an of-this-world biologic pandemic, the authors conclude, "An outbreak of zombies infecting humans is likely to be disastrous, unless extremely aggressive tactics are employed against the undead." Eradicating the zombies, which requires removing the head or destroying the brain, is not predicted by their formulas—unless attacks are "sufficiently frequent" and with "increasing force."

The best possible scenario is humans coexisting with zombies in some kind of equilibrium. The 2 big problems with zombie-ism are that a) there is no immunity and b) the dead can always rise. Also, if the zombie attack is prolonged, the authors predict that zombies will completely eradicate humans; ongoing human births and deaths will provide the zombies with a limitless supply of infectees. (But this doomsday scenario begs the question: What happens when the world is populated solely by zombies?)

The authors propose that their mathematical models may be applied practically to cases of "allegiance to political parties" (heh-heh, way to slide one in) or infectious diseases with a dormant phase.

* Okay, I really have no idea. The authors could be totally cool operators, with children (ie, zombie noshes) peppering the globe.

Zombies from Night of the Living Dead from Wikipedia.

Addendum: The "?" after the anchor author's name (Robert J. Smith?) is evidently not a typo.

As of August 6th, the World Health Organization reports 1462 deaths due to the novel H1N1 swine-flu virus among a global total of 177,457 cases, for an overall mortality rate of 0.82%. The death rate as of July 31st, was 0.71%, which is up more than 60% from mid-June. Among the tabulated deaths, a steady 87% (1462) have occurred in the Americas.

Preliminary data from the CDC

The CDC determined the following sensitivities of 3 commercially available RIDTs by using respiratory specimens that were positive for the novel H1N1 virus with rRT-PCR. However, the CDC advises against discriminating among the 3 tests' sensitivities, because of the relatively low number of specimens analyzed.

* n = 34.

The sensitivities of the RIDTs declined in proportion to declining titers of novel H1N1. Factors that affect influenza titers in specimens include the timing of specimen collection during illness, the age of the patient, the type of specimen collected, and the transportation and storage of the specimen.

The overall sensitivities of the RIDTs for seasonal H1N1 (n = 5) or seasonal H3N2 (n = 15) were observed to be 60%-80% and 80%-83%, respectively. (It is important to note that RIDTs do not distinguish among subtypes of influenza A virus.) The CDC advises that the results of RIDTs should be interpreted in the context of known circulating viral strains and provides this link for guidance.

N. B.—The sensitivity and specificity of the rRT-PCR assay, when compared with the reference standard of viral culture, are 99.3% and 92.3%, respectively.

08/13/09 update: RIDT data from the Naval Health Research Center indicate respective sensitivities of 51% for the detection of novel H1N1 (n = 39 patients), 63% for seasonal H1N1 (n = 19), and 31% for H3N2 (n = 19). Specificities for all influenza A virus types were 99%. Values are for the QuickVue Influenza A+B test; the reference standard is rRT-PCR. 

As of July 31st, the World Health Organization reports 1154 deaths due to the H1N1 virus among a global total of 162,380 cases, for an overall mortality rate of 0.71%. Consequently the H1N1 death rate has increased more than 60% after holding steady at about 0.44% since mid-June. The current H1N1 death rate also surpasses the death rate from early June (0.66%). Among the tabulated deaths, 87% (1008) have occurred in North and South America.

Elimination of trachoma** was achieved by using the so-called SAFE strategy of the World Health Organization—which includes eyelid surgery, antibiotics (ie, azithromycin), facial cleanliness, and environmental improvements. The strategy was used successfully 3 years ago to wipe out trachoma in Iran, Morocco, and Oman and is the basis of the WHO's Alliance for the Global Elimination of Blinding Trachoma by the year 2020.

Azithromycin (Zithromax) is currently being donated by Pfizer, in conjunction with the Edna McConnell Clark Foundation. The drug company and the foundation originated the International Trachoma Initiative in 1998.

* Caused by the bacteria Chlamydia trachomatis.

** Defined by WHO as 1) elimination of blinding cases of trachomatous trichiasis through surgery (or at least offering surgery to all cases); 2) reducing cases of trachomatous follicular conjunctivitis in adults to fewer than 1 per 1000; and 3) reducing the prevalence of trachomatous follicular conjunctivitis in children (age range, 1-9 years) to less than 5%.

Image of trachomatous conjunctival scarring from WHO trachoma grading cards.

WHO reports that the "overwhelming majority" of H1N1 cases have been mild, with spontaneous recovery, despite the fact that the virus has spread with "unprecedented speed." Confirming these cases with laboratory testing, however, is "extremely resource-intensive," WHO writes. "In some countries, this strategy is absorbing most national laboratory and response capacity, leaving little capacity for the monitoring and investigation of severe cases and other exceptional events."

For countries well ensconced in the H1N1 pandemic, surveillance procedures will now mirror those used to assess seasonal influenza activity. Countries with "well-established laboratory-based surveillance systems" will monitor any changes in the H1N1 virus.

According to WHO's most recent (and last) global update, on July 6, a total of 94,512 H1N1 cases had occurred throughout 135 countries or territories. The overall mortality rate remains steady, at 0.45% (429 deaths).

H1N1 cases have now been reported in 120 countries or territories, and related deaths have occurred in 17. Countries disproportionately affected by new cases (where more than 500 cases have occurred) include Thailand, the United Kingdom, Brazil, Peru, and Spain. The number of swine flu deaths in the United States now surpasses those in Mexico.

The World Health Organization reports a total of 52,160 cases of H1N1 disease (up from 27,727) in 99 countries (up from 74), with a large bulk of new cases reported in the United States (3594) and Chile (1190). The number of deaths stands at 231 (up from 141), for an overall mortality rate of 0.44%.* Swine-flu-related deaths have now affected 11 countries.

* Which is slightly less than the previously calculated mortality rate of 0.5%. 

While drugmakers create a vaccine against the currently pandemic swine-flu virus (H1N1 S-OIV 2009), neurologists are advised to monitor the safety of such inoculations, should they be implemented. The caution is founded on a higher-than-expected rate of Guillain-Barre syndrome (GBS) in vaccine recipients during the 1976 immunization campaign against swine flu, reports Neurology Today.

More than 30 years ago, soldiers at Fort Dix, New Jersey, experienced an outbreak of swine flu. Fearing a recurrence of the 1918 influenza epidemic, US government officials implemented a widespread vaccine campaign in which more than 40 million Americans were immunized. However, the drive was aborted after 3 months when reports of GBS in vaccinated individuals emerged. Although GBS surveillance data for the time period are sketchy, evidence suggests that vaccine recipients were significantly more likely to develop the condition within several weeks after inoculation.*

At present, leading neurologists do not anticipate a government-led vaccine campaign against H1N1 S-OIV 2009, given the low mortality rate (0.5%) of the current swine-flu pandemic and the historical risk of GBS with inoculation.

* The typical background rate of GBS is about 1.5 per 100,000 individuals.

As of yesterday, 74 countries had reported a total of 27,727 cases of swine flu, the majority of which have occurred in Mexico and the United States. But the virus has caused only 141 deaths, for an overall mortality rate of about one half of 1%.

Swine flu in humans first emerged in Mexico last April; although Oxford scientists estimate that the H1N1 virus could have been transmitted from pigs to people as early as August of last year, writes the AP.

A case of nonfatal hemorrhagic fever due to Lujo virus also occurred in a South African nurse, who cared for one of last year's deceased victims. The nurse evidently responded to ribavirin treatment and has completely recovered. Human-to-human transmission of Lujo virus is believed to be through contact with infected body fluids. How the index case acquired infection is unknown, but disease-causing arenaviruses are typically transmitted from rodent vectors.

* A Zambian safari employee (index case), a South African paramedic, a South African nurse, and a South African hospital employee.

Photo of house mouse (Mus musculus), which is the rodent vector for the Old World arenavirus, lymphocytic choriomeningitis virus, from Wikipedia.

By drawing on data from a nationwide inpatient database,* the CDC found pediatric hospitalization rates (per 1000 children) for all-cause pneumonia and nonpneumonia acute respiratory illness (ARI) as follows:

According to the report, the rate reduction for all-cause pneumonia in 2006 represented an estimated 36,300 fewer hospitalizations for children younger than 2 years of age (when compared with the 1997-1999 period). Likewise, the rate reduction for nonpneumonia ARI in 2006 represented an estimated 51,500 fewer hospitalizations in the same age group.

Rate reductions for all-cause pneumonia in children aged 2-4 years were not observed, despite the fact that rates of invasive pneumococcal disease have definitely decreased in this age group since the introduction of PCV7. The authors speculate that organisms other than Streptococcus pneumonia may be more common causes of pneumonia in this age group.

Nevertheless, these data suggest that the benefits of PCV7 extend beyond those of reducing the incidence of invasive disease that is known to be due to S. pneumonia (although the CDC stresses that a causal relationship between vaccination and hospitalizations has not been established).

The concomitant decline in the rates of nonpneumonia ARI among children younger than 2 years of age indicates that the reduction in hospitalizations for all-cause pneumonia is not due to a shift in coding behavior. One explanation for this reduction is that S. pneumoniae may contribute to a wider range of childhood respiratory illnesses than previously thought. Data from trials assessing a 9-valent PCV in Israel and South Africa support this conjecture.

* The Nationwide Inpatient Sample, which contains data on inpatient stays from states that participate in the Healthcare Cost and Utilization Project. Information for roughly 8 million hospitalizations in 2006 was recorded.

Scanning electron micrograph of S. pneumoniae from the CDC/Dr. Richard Facklam.

The surveillance group identified 1379 cases of pneumococcal meningitis during the study period, in patients aged 2 days to 93 years. The case fatality rate in children was 8.4%, and that in adults was 22.3%. Fatality rates were similar in HIV-positive and HIV-negative adults.

From 1998-1999 to 2004-2005, the incidence of pneumococcal meningitis (cases per 100,000 persons) caused by PCV7 serotypes or PCV7-related (ie, cross-reactive) serotypes declined significantly overall, and rates of PCV7-serotype meningitis declined significantly in the youngest and oldest subpopulations. However, the relative incidence of meningitis caused by non-PCV7 serotypes during this time increased significantly—especially in children younger than 2 years of age. Particularly concerning is the rise of non-PCV7 strains that are not susceptible to antibiotics, report the authors.

Table. Cases of Pneumococcal Meningitis per 100,000 Persons

Vaccination with PCV7, which covers 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), is currently recommended by the Advisory Committee on Immunization Practices for all US children aged 2-23 months and for children aged 24-59 months who are at increased risk of pneumococcal disease (eg, those with sickle cell disease or HIV). The vaccine was licensed in 2000 and is intended for children younger than 2 years of age, because the (old-as-dirt) 23-valent pneumococcal vaccine (eg, Pneumovax; Merck) does not protect this age group (who demonstrate the highest rate of pneumococcal disease). Also Pneumovax does not reduce nasopharyngeal colonization with pneumococci, a primary mode of bacterial transmission.

The authors report the following coverage with PCV7 in US children aged 19-35 months during 2006: ≥4 doses, 68%; ≥3 doses, 87%. Previous data have shown a reduction in the incidence of invasive pneumococcal disease generally (but not pneumococcal meningitis specifically) since the licensing of PCV7.

In development are 2 pneumococcal conjugate vaccines with additional serotypes: PCV10 and PCV13. PCV10 includes the PCV7 serotypes plus 1, 5, and 7F, which would have covered 27% of meningitis cases in 2004-2005, claim the authors. PCV13, with the PCV10 serotypes plus 3, 6A, and 19A, would have covered 50% of cases.

HIV = human immunodeficiency virus; PCV = pneumococcal conjugate vaccine.

* Caused by Streptococcus pneumoniae.

** San Francisco County, CA; CT; 20-county Atlanta, GA, area; 6-county Baltimore, MD, area; 7-county area in MN; 7-county Rochester, NY, area; 3-county Portland, OR, area; and 5 urban counties in TN (N > 18 million).

Scanning electron micrograph of S. pneumoniae from the CDC/Dr. Richard Facklam.

In a country checked by stratospheric inflation and political corruption, a persistent cholera epidemic in landlocked Zimbabwe has now taken more than 1700 lives and sickened 35,330, according to the latest report from the World Health Organisation.

Since August 2008, the epidemic has affected all provinces in the country, reveals WHO; however, a large percentage of cases have been documented in Budiriro, a congested suburb of Harare, and in Beitbridge, a border town with South Africa. The overall fatality rate of disease is reported at 4%, but death rates have escalated to 20%-30% in remote areas.

The organization Medecins Sans Frontieres (Doctors Without Borders) reports a "clear shift" in cholera cases from Zimbabwe's urban areas to suburban and rural towns, which logistically confounds disease management. Nevertheless, unlike WHO, MSF reports an overall decrease in the number of cholera cases in Zimbabwe. MSF suggests that tally differences between the 2 organizations may be a function of the spread of disease and disease-reporting capabilities. Sources cited at Wikipedia indicate that the cholera epidemic has spread to neighboring countries Botswana, Mozambique, South Africa, and Zambia.

Cholera, caused by the bacterium Vibrio cholerae, is primarily transmitted through contaminated food or water. The characteristic symptom of copious, watery diarrhea, caused by the bacterial enterotoxin, can lead to death through dehydration. The collapse of clean water supplies, sanitation measures, and garbage collection in Zimbabwe are aggravating factors of the epidemic. Professional medical care in Zimbabwe has also been stymied by the country's economic crisis. To top it off, the rainy season began in November.

WHO currently urges proper food safety and personal hygiene, as well as the use of oral rehydration salts to reduce the mortality risk associated with cholera. Prophylactic antibiotics are discouraged, and once an outbreak has begun, the "internationally available WHO prequalified oral cholera vaccine" is not recommended. (The parenteral cholera vaccine was never recommended by WHO because of its low efficacy and risk of adverse events.)

Map showing spread of cholera in Zimbabwe as of December 6, 2008, from Wikipedia.

 ...before looking forward.

Pathophilia's Top 10 Medical Stories of 2008: A Recap

10. Gunvalson v. PTC Therapeutics

9. California v. Roozrokh and Cardiac-Death Organ Donation

8. Hand, Foot, and Mouth Disease in China

7. Continuing Backlash Against Pharma

6. Media Obsession With Delayed Results of ENHANCE Trial

5. Investigational Drugs for Alzheimer's Disease Disappoint

4. Milder Rotavirus Season Coincides With Vaccine Uptake

3. USAMRIID Scientist Identified as Sole Perpetrator of "Anthrax Letter Attacks"

2. Resurgence of Measles

1. Intentional Drug and Food Tampering in China

Other notable stories of 2008 that didn't make Pathophilia's totally arbitrary list:

• More cases of progressive multifocal leukoencephalopathy (PML) with Tysabri (natalizumab) use
• Pig-slaughter neuropathy
• US government compensates Poling family for vaccine-related autism
• Ted Kennedy diagnosed with glioblastoma multiforme

In the United States, a significantly milder rotavirus season coincided with increasing uptake of the rotavirus vaccine.

The onset of the most recent 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 in the United States. These surveillance data coincide with increasing administration of the rotavirus vaccine (RotaTeq; Merck) in infants, according to a June report in 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.

According to the CDC, mean coverage in the United States with 1 dose of rotavirus vaccine among 3-month-old infants increased from 49% in May 2007 to 56% in May 2008. In 13-month-old infants, mean coverage with 3 doses increased from 3.4% in May 2007 to 33.7% in May 2008.

Percentage of Positive Rotavirus Tests From NREVSS
(Data from 2008 are current through May 3)

In the United States, rotavirus historically causes up to 70,000 hospitalizations, 272,000 ED visits, and 410,000 office visits in each year. Worldwide, roughly 40% of hospitalizations for diarrhea in children younger than 5 years of age are caused by rotavirus, according to a November report in the MMWR. More than half a million young children die each year from rotavirus-induced diarrhea, and 85% of these deaths occur in low-income African or Asian countries.

Rotavirus vaccines (Rotarix; GSK Biologicals or RotaTeq) confer 85%-98% protection against rotavirus diarrhea. These vaccines have been incorporated into the routine immunization programs of an increasing number of countries, and trials in low-income Asian and African countries are ongoing. Notably these vaccines confer protection against rotavirus serotypes that are not included in their respective formulations. 

Transmission electron photomicrograph of intact rotavirus particles from the CDC.

From January 1 to May 9, at least 61,459 children contracted the disease, caused by enterovirus 71 (EV71), according to the Chinese Center for Disease Control and Prevention and the WHO Representative Office in China. As of mid-May, at least 43 children (typically infants or toddlers) died as a result. Hardest hit were the mainland provinces of Guangdong, Anhui, Zhejiang, Shandong, and Henan. The infection was especially concentrated in Fuyang City, in the eastern part of the Anhui province, where thousands of children were hospitalized and most of the deaths occurred.

HFMD is a common and usually mild childhood disease, caused by coxsackie virus A16 or EV71; although EV71-related HFMD can manifest infrequently as encephalitis or poliomyelitis-like paralysis. Outbreaks of EV71-related HFMD throughout southeast Asia and Australia have been documented since 1997, but the disease had not affected mainland China to any significant extent before this year (or at least as far as anyone outside of China knows). There are indications that this year's major epidemic, which reportedly began in March, was exacerbated by the slow reporting of escalating cases from local health officials. 

A smaller outbreak of HFMD occurred in the Fujian province in October. Contemporary news reports indicate that 113 children became ill, and 3 infants died (all of whom were younger than 1 year of age)

Treatment of the highly contagious HFMD consists of supportive, symptomatic care. Because there is no available vaccine, prevention relies on appropriate hygienic measures, particularly handwashing. A nationwide personal-hygiene campaign was reportedly instigated in China during the Spring epidemic. The Xinhua News Agency indicated that traditional Chinese medicine was also urged by local health authorities, including "a recipe involving a number of Chinese herbs that must be used continuously for at least 7 days."

For more background, read these Pathophilia posts:

• Continuing Outbreak of Hand, Foot, and Mouth Disease in China
• Hand, Foot, and Mouth Disease Takes More Lives in China
• Chinese CDC/WHO Release Report on Hand, Foot, and Mouth Disease

Also an official report of the major HFMD epidemic in China is available here.

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.

The latest data were derived from a WHO surveillance program in 35 countries in Africa, Central and South America, Eastern Europe, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Detection was based on an enzyme immunoassay for rotavirus antigen in stool samples, and strain genotypes were identified by RT-PCR. The most common strains, excepting those in the Eastern Mediterranean region and Africa, were G1P[8], G9P[8], and G2P[4]—which accounted for two thirds of the strains detected.

In trials in the Americas and Europe, 2 live, oral rotavirus vaccines—an attenuated G1P[8] human rotavirus vaccine (Rotarix; GSK Biologicals) and a live, pentavalent, human-bovine (WC3 strain) reassortment vaccine containing serotypes G1, G2, G3, G4 and P[8] (RotaTeq; Merck)—conferred 85%-98% protection against rotavirus diarrhea. These vaccines have been incorporated into the routine immunization programs in 11 countries in these regions and in Australia. Trials of these vaccines in low-income Asian and African countries are ongoing. Notably these vaccines confer protection against rotavirus serotypes that have not been included in their respective formulations.

The CDC recommends 3 doses of an FDA-approved rotavirus vaccine** between the ages of 6 and 32 weeks. An interim report indicates that, for the 2007-2008 rotavirus season in America, viral activity started much later and was much less extensive than in previous years. These changes are believed to be due to the uptake of rotavirus vaccine.

According to the MMWR, more than half a million young children in the world die each year from rotavirus-induced diarrhea; 85% of these deaths occur in low-income African or Asian countries.

* Younger than 5 years of age.

** The tetravalent rhesus-human reassortment rotavirus vaccine (RotaShield; Wyeth) was voluntarily withdrawn from the market in 1999 owing to a low, but increased, risk of intussusception.

Transmission electron photomicrograph of intact rotavirus particles from the CDC.

According to the CDC, HepB coverage—especially within 24 hours after birth—is hampered in endemic areas by limited access (for instance, among infants born at home in remote areas), poor training or coordination among maternal healthcare workers, inadequate delivery of the vaccine (which requires cold storage), and the use of combination vaccines (eg, the Haemophilus influenza type b and HepB vaccine), which cannot be administered at birth. In 2006, 46% of the world's infants were born in countries where chronic infection with hepatitis B virus is historically high.

The major routes of HBV transmission in infancy include maternal transmission during delivery and infection from household contacts. The risk of developing chronic HBV disease among infected infants is very high, 90%, and the risk of premature death due to cirrhosis or liver cancer (photo) with chronic HBV is 25%, according to the CDC. Perinatal infection with hepatitis B virus causes nearly one quarter of the world's 620,000 HBV-related deaths each year.

The CDC recommends vaccination with monovalent HepB in all newborns before hospital discharge and within 12 hours of birth if the mother is positive for hepatitis B surface antigen or her status is unknown. A monovalent or combination vaccine containing HepB is administered at 1-2 months of age, and a final dose is given at 6 months of age or later.

HBV = hepatitis B virus; UNICEF = United Nation's Children's Fund; WHO = World Health Organisation.

* Defined as ≥8% in the general population and includes 87 countries: 45 in Africa; 23 in the Western Pacific; 10 in Europe; 5 in Southeast Asia; and 4 in the Eastern Mediterranean. 

Photo of Cambodian woman with hepatocellular carcinoma due to chronic HBV infection from the CDC.

Since September 1, 43 cases of pertussis have been reported in Springfield, OH. The ages of those affected range from 2 months to 74 years; however, most cases have occurred in children aged 7-10 years. In 2007, 4 cases of whooping cough were documented in Clark County, OH, and 7 occurred in 2006. A report earlier this month indicates that 631 cases of pertussis have occurred in the state this year, as of November 8.

A total of 27 pertussis cases, mostly in children, were reported in 8 counties throughout South Dakota during the last month. In Nebraska, 125 cases of the disease have been confirmed so far this year, with 48 recent cases in the area of Omaha and 5 in distant Lincoln County. In 2007, 70 cases of pertussis were reported in the entire state. More than a dozen people have been diagnosed in Clarke County, IA, with pertussis, and an unspecified number of cases of whooping cough have occurred this fall in west-central Minnesota.

Outside of the Midwest, recent pertussis outbreaks have been reported in North Carolina, Arkansas, Tennessee, Kentucky, New York, and Texas. High schoolers and adults have been affected, as well as children and infants. Older individuals typically have milder disease, but they serve as a vehicle for transmission of the infectious agent to the less protected (see news video here). Those most susceptible to pertussis complications are children younger than 12 months of age and those who are incompletely immunized. According to the CDC, the incidence of pertussis has increased steadily in the United States since the 1980s.

Pertussis is highly contagious, and human-to-human transmission occurs by means of respiratory droplets. The CDC indicates that the average incubation period of the bacterium is 7-10 days, but may be longer. For 1-2 weeks, nonspecific upper respiratory symptoms are typical (excepting some infants), followed by development of the characteristic, paroxysmal whooping cough, which can persist for 2-6 weeks. Vomiting and syncope may accompany the powerful cough, particularly in children. Common complications of the cough include pneumothorax, epistaxis, subconjunctival hemorrhage, subdural hematoma, hernia, rectal prolapse, urinary incontinence, and rib fracture. Antibiotic treatment (eg, erythromycin) of pertussis primarily mitigates spread of the disease. Convalescence, with a nonparoxysmal cough, may take another 2-6 weeks or longer. Affected individuals are susceptible to superimposed viral or other bacterial respiratory infections.

Immunity against the causative agent, the bacterium Bordetella pertussis, is obtained through vaccination; although protection is not absolute.* The DTaP vaccine is administered at 2, 4, 6, and 15-18 months of age and at 4-6 years of age. The Tdap vaccine is recommended at 11 or 12 years of age and in place of at least one 10-year tetanus booster between the ages of 19 and 64 years. A study published in this month's Pediatrics indicates that giving the first DTaP vaccine dose at 6 weeks, instead of 2 months, would prevent approximately 1200 cases of the disease, nearly 900 related hospitalizations, and 7 deaths.

DTaP = diphtheria, tetanus, acellular pertussis; Tdap = tetanus, reduced dose of diphtheria, reduced dose of acellular pertussis.

* According to a CDC report from 2005, pertussis vaccine effectiveness is 84% with 1 or 2 doses, 96% with 3 doses, and 98% with 4 or more doses. Vaccine effectiveness may be enhanced in persons who receive more than 1 type of vaccine (ie, DTP for doses 1-3 and DTaP for dose 4).

Picture of boy diagnosed with pertussis, aka whooping cough, from the CDC.

Addendum: A comparison of monthly data for reported pertussis cases in 2006 and the Google Trends feature for the same year (search terms, "pertussis" and "whooping cough") suggests that the Google feature works better for tracking influenza.

The latest nifty service from the company, and specifically from its nonprofit arm, Google.org, is a graphic flu tracker, based on the use of web search terms (through Google's search engine, no doubt) by geographic location (that is, a user's IP number). Google created the tracker after observing that the rise in influenza cases, as documented by the CDC, paralleled the search for relevant information on the web. But unlike the CDC's surveillance information, Google's program anticipates influenza trends ahead of the CDC's retrospectively reported case data. An explanation of how the thing works is provided here.

The WSJ Health Blog reports that Google Trends offers the opportunity to monitor any geographic time-trend in Google's web searches, whether it's for "botulism" or "brangelina."

Buried in last week's election news is a NYT update on the newly discovered African arenavirus, which killed a Zambian safari employee, a South African paramedic, and a South African nurse. The paramedic and the nurse both had close contact with the Zambian index case.

A fourth fatality is now reported as a woman who cleaned the South African hospital room of the index case. Another South African nurse, who cared for the paramedic, also became critically ill with the infection, but she responded to early treatment with the antiviral drug ribavirin, according to the paper.

The manner in which the index case became infected with the virus is unknown; however, arenaviruses are generally transmitted in the aerosolized, dried urine of infected rodents. Person-to-person transmission is presumed to be through contact with body fluids or respiratory droplets.

The small outbreak of the new arenavirus is believed to be isolated to these 5 cases.

Photo of house mouse (Mus musculus), which is the rodent vector for the arenavirus lymphocytic choriomeningitis virus, from Wikipedia.

September 12: An employee at a Zambian safari-tour company, Cecilia "Silky" van Deventer, 36, is airlifted from a Lusaka hospital to South Africa for management of an acute, unknown illness characterized by high fever and a deteriorating mental state. Prodromal symptoms included fever, headache, diarrhea, and myalgias for approximately 7 days. Van Deventer is presumed to be suffering from "tick-bite fever," given her contact with horses.

September 14: Van Deventer dies at the Morningside Medi-Clinic, a 230-bed private hospital in Sandton, near Johannesburg.

September 27: Paramedic Hannes Els, 33, who assisted in the evacuation of van Deventer from Zambia to South Africa is admitted to a Johannesburg hospital. Prodromal symptoms are similar to those of van Deventer, according to WHO.

October 1: An ICU nurse, Gladys Mthembu, 34, who cared for van Deventer in South Africa, is admitted to Sir Albert Robinson Hospital in the West Rand for similar symptoms.

October 2: Paramedic Els dies.

October 5: Nurse Mthembu dies.

October 13: Test results from the National Health Laboratory Service in Johannesburg and the CDC in Atlanta indicate that the causative agent is a newly identified arenavirus.* WHO reports that another South African nurse, who cared for either Els or Mthembu, has become ill with the disease (virus is confirmed by PCR). Latest reports indicate that the nurse is in stable condition in hospital isolation.

October 15: Sowetan reports that a radiographer, who worked at Morningside Medi-Clinic and came into contact with van Deventer, is admitted to St. Augustine's Hospital in Durban with arenavirus symptoms. There are doubts, however, about whether the radiographer is infected with the newly recognized virus.

WHO indicates that contacts of the fatal cases, 121 in South Africa and 23 in Zambia, are being traced. Person-to-person transmission of the virus (usually in the healthcare setting) is believed to occur primarily through contact with body fluids, as in the case of Lassa virus. Therefore an epidemic of the new virus is not expected.

Online posts and other news reports suggest that there is contention between Zambians and South Africans about the origin of the virus and the nationality of the index case, van Deventer.

* In the same family as viruses that cause Lassa fever and lymphocytic choriomeningitis. The most common vector for members of this virus family is rodents.

Photo of house mouse (Mus musculus), which is the rodent vector for the arenavirus lymphocytic choriomeningitis virus, from Wikipedia.

What is Balamuthia mandrillis?
A free-living amoeba in soil.

How is disease transmitted?
Airborne cysts are inhaled, or skin lesions are directly contaminated.

Who or what is affected?
Immunocompetent or immunocompromised humans, nonhuman primates, horses, dogs, and sheep. People with occupational or recreational exposure to soil (agriculture, construction, dirt biking) may be especially vulnerable.

What are disease symptoms?
Those consistent with other forms of encephalitis—eg, fever, encephalopathy, cranial nerve palsies, seizures.

What does the CSF look like?
Markedly elevated protein (>100 mg/dL); elevated WBC with a predominance of lympocytes; normal or low glucose.

What does brain MRI look like?
Typically abnormal. In the California cases, multiple ring-enhancing lesions, white matter lesions, hypointense lesions, or hydrocephalus were noted.

How is disease definitively diagnosed?
Indirect immunofluorescence staining of formalin-fixed tissue—eg, brain. PCR testing for Balamuthia DNA in CSF or brain tissue has been used; although, the specificity and sensitivity of PCR testing for Balamuthia are unknown, as are the specificity and sensitivity of serologic testing.

Where are reference laboratories? 
At the CDC (gsv1@cdc.gov) and the California Department of Public Health (shilpa.gavile@cdph.ca.gov).

What is the treatment?
Three surviving patients in the United States received pentamidine isethionate, fluconazole, flucytosine, sulfadiazine, and a macrolide antibiotic (azithromycin or clarthromycin).

What is the survival rate?
In the California cases, approximately 10%.

Who or what is Balamuth?
Balamuthia co-discoverer Govinda S. Visvesvara, PhD, of the CDC, writes by e-mail that the organism was named after his major advisor, William Balamuth (1914-1981), Professor of Zoology at UC Berkeley. How's that for homage?

Photomicrograph of Balamuthia mandrillis trophozoites in brain tissue from the CDC.

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)

According to the CDC, the mean coverage with 1 dose of rotavirus vaccine among 3-month-old infants was 49% in May 2007 and 56% in May 2008. In 13-month-old infants, mean coverage with 3 doses was 3.4% and 33.7% in May 2007 and May 2008, respectively. Rotavirus, the leading cause of severe, acute gastroenteritis in young children worldwide, results in up to 70,000 hospitalizations, 272,000 ED visits, and 410,000 office visits in the United States each year.

*Data are from Monroe County, NY; Hamilton County, OH; and Davidson County, TN.

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.