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CIDRAP- H7N9 cases found by routine surveillance trended younger, milder

Shiloh

Editor, Senior Moderator
Source: http://www.cidrap.umn.edu/cidrap/content/influenza/h7n9/news/jun2513mild-br.html


H7N9 cases found by routine surveillance trended younger, milder

Lisa Schnirring * Staff Writer

Jun 25, 2013 (CIDRAP News) ? A report on five Chinese H7N9 cases that were detected during routine flu surveillance reveals that the patients had milder infections and were younger than most, shedding new light on the spectrum of illness and the challenges officials could face in controlling the disease.

China is thought to have a good influenza surveillance system, and the report yesterday in the British Medical Journal (BMJ) provides a useful look behind the curtain on how they monitor flu, especially during an outbreak of an emerging infections.

The five surveillance detections were included in the 130 H7N9 infections reported by China as of May 27. The country reported 131 cases overall, and Taiwan has reported one infection, putting the total outbreak number at 132. So far 39 patients have died from their illnesses.

China's national sentinel surveillance system includes 554 hospitals across the mainland's 31 provinces. Influenza-like illnesses are reported weekly to the China Centers for Disease Control and Prevention (China CDC). At each site, 10 to 15 nasopharyngeal swabs are collected weekly in convenience sampling of patients who have had flu-like illness with fever for no longer than 3 days and have not had antiviral drugs.

Outpatient clinics and emergency departments are the first step for sick patients, because of China's national health insurance coverage and the lack of stand-alone clinics, according to the report.

Three of the five H7N9 patients were young children, and the ages ranged from 2 years to 26 years. Four were male, and all lived in urban areas in three provinces. Their symptom onsets ranged from Mar 17 to Apr 26. Four had been exposed to live animals, including chickens.

All of the patients had fever and upper respiratory tract infections, and all had mild-to-moderate H7N9 infections and quickly recovered. Two patients were hospitalized, one of whom had pneumonia that didn't require intensive care. Close-contact monitoring turned up no additional cases.

The researchers wrote that the case series presents a contrast to the more severe clinical infections that have been reported so far. Though the mild cases and severe cases shared some epidemiologic features, such as location and exposure history, they also had important differences. The five patients found through surveillance were younger and had no underlying medical conditions.

Analysis of the surveillance-detected cases shows that H7N9 infections can have diverse presentations, requiring vigilance among health workers and public health teams, the authors said.

"A large proportion of unidentified cases with mild infection in the community may be a source of infection to other susceptible people if H7N9 develops the capacity for human-to-human transmission," they wrote, adding that the pattern could make the disease more difficult to control.

Ip DKM, Liao Q, Wu P, et al. Detection of mild to moderate influenza A/H7N9 infection by China's national sentinel surveillance system for influenza-like illness: case series. BMJ 2013 Jun 24;346 [Abstract]
 
Re: CIDRAP- H7N9 cases found by routine surveillance trended younger, milder

Scalability Questions
Around
Rate of Mild Case Detection

RePublished from BMJ. Detection of mild to moderate influenza A/H7N9 infection by China?s national sentinel surveillance system for influenza-like illness: case series [Thread#207942]:

Post#3
The number of assumptions is skyrocketing as the number of possible cases. And this is not much informative.

554 sentinel points
12.5 swabs per week / point
554*12.5*4 wk=27,700 swabs per month

5 sentinel swabs tested positive for H7N9 from the above paper =

5 / 27,700 = 0.02% positivity rate

If in a 5,000,000 China megacity during the same period of time there was an ILI rate of 14 x 1,000 then:

14 : 1,000 = x : 5,000,000

x = 70,000 ILI cases per week

if these ILI cases should have been swabbed - employing the above positivity rate we should have had:

70,000 * 0.02% = 14 H7N9 cases

Scaling

Scaling statistics using national factors onto discrete (sub-component) populations is not generally held as an ideal mechanism for creating actionable results at the discrete population level. When this type of spreading is undertaken at a giga-scale (i.e. population of China), often additional considerations and cautions must be employed. The types of projections are the purest form of invention.

An inspection of significant digits may be in order for these calculations while keeping at the forefront the fact that averages and assumptions are being multiplied by averages and assumptions. We will examine here the individual factors and the calculation veracity. Projection estimates will be provided at the end of this post for your example population of 5 million and for several actual geographies in China related to emergent H7N9.

You certainly are accurate on the skyrocketing effect of assumptions. One paper that you posted requires a minimum of 15 swabs per week and this paper suggests a quota range of 10 to 15 swabs per week, a ceiling 50% above the floor (substantial variance, σ sqared=6.25). Using actual counts from the earlier study (46,807 swabs from 554 locations over 8 weeks) gives an average of 10.56115 swabs per location per week.

Factor Validity

The authors openly admit that swabbing is not random and then they immediately attempt without any observational evidence to attach the idea that this quota-driven, non-random test is unbiased? They pledge that their system, though structured with a non-randomised collection, is representative of a billion count population? The system begins by missing 97.5% of the hospitals (sampling 2.5%) and then proceeds to require 15 swabs per week, but only gets about 10.56115 across a week's duration. We're not certain if the authors have supplied a supplement denoting the actual geographic collections? If an attempt is being made to differentiate disease epidemiology, then we'll need specific geographic counts rather than obtuse gerrymandering accumulations and averages.

Severity bias is generally present in infectious disease collections that are not intentionally randomised.

Test Duration

Is the test duration for this paper defined or are we to assume that the accumulations take place over the entire emergence period from their first publicly reported case in late February until May 27? If so, then 12 weeks very much dilutes the outcome when used in place of the 4 week estimate to accommodate the 5 mild cases discovered via passive surveillance of ILI reports. Early multipliers reduced by 66.67% dampen results.

Emerg Infect Dis. Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China [Thread #205425, Post#1] (emphasis mine)

On April 3, 2013, to enhance surveillance for influenza A(H7N9) virus, all network laboratories were required to increase the number of specimens to a minimum of 15/week and to test all specimens collected since March 4, 2013, for influenza A(H7N9) virus by real-time reverse transcription PCR . . .
. . .
During March 4?April 28, CNISN tested 46,807 nasopharyngeal swab samples from 554 sentinel hospitals throughout mainland China.

ReCalculation

Information Quality is very low in the emergent H7N9 discussion though Information Quantity sometimes exceeds necessity.

Using the actual numbers from the previous study (46,807 covering 8 weeks from early March to late April) summed with the mandated 15 swabs per week per hospital (33,240 covering 4 weeks from late April to late May), we estimate the denominator to be a minimum of 80,047 total swabs over 12 weeks. With detection of 5 mild cases, the rate calculates to:

Mild Case Detection Rate for Emergent H7N9 in ILI Cases ~ 0.006246329%.

Holding constant the ILI factor discussed of 0.01400 (14 Reports per 1,000 Population), the following selected geographic projections may be discussed based on the limitations of the incoming factors' veracity. Particularly daunting is the non-applicability of a national Mild Case Detection Rate across disparate, sub-state geographies.

Concentrated City
Population . . . . . 5,000,000
Projected ILI . . . . . .70,000
Projected Mild H7N9 Count___4.4

Beijing
Population . . . . 20,690,000
Projected ILI . . . . .289,660
Projected Mild H7N9 Count__18.1

Shanghai
Population . . . . 23,470,000
Projected ILI . . . . .328,580
Projected Mild H7N9 Count__20.5

Guizhou Province
Population . . . . 34,690,000
Projected ILI . . . . .485,660
Projected Mild H7N9 Count__30.3

Fujian Province
Population . . . . 37,200,000
Projected ILI . . . . .520,800
Projected Mild H7N9 Count__32.5

Zhejiang Province
Population . . . . 54,630,000
Projected ILI . . . . .764,820
Projected Mild H7N9 Count__47.8

Jiangsu Province
Population . . . . 78,990,000
Projected ILI . . . 1,105,860
Projected Mild H7N9 Count__69.1

China
Population . . 1,344,000,000
Projected ILI . . .18,816,000
Projected Mild H7N9 Count__1,175.3

As Chris & Edgar like to say, "Caveat Lector."

Genetic Calibration

We do tend to agree with the authors that cross-referencing the actual disease (gene form) to the statistics is potentially beneficial for the public.

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