Community Acquired Infection of unknown focus in Infants and Children ( not on NICU ) - Management of

Publication: 28/11/2011  
Last review: 06/07/2017  
Next review: 06/07/2020  
Clinical Guideline
CURRENT 
ID: 2671 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Management of community-acquired infection of unknown focus in Infants and Children between 4 weeks and 16 years old (not on NICU)

Summary
Community Acquired Infection of unknown focus in Infants and Children ( not on NICU )

Management Pathway Flowchart/ Overview

Inclusion criteria:
Temperature (>37.8oC, OR examination evidence of febrile illness)
AND, No focal source of infection evident from history or examination
AND, No other more appropriate pathway (community acquired pneumonia, central venous catheter infections, CNS infection…)

  • WARNING - infants and children with an open fontenelle are unlikely to have classic symptoms and signs of meningitis

Action: Record weight, observations, PAWS and enter pathway corresponding to history, examination and PAWS score

Table 1. Summary of red, yellow and green clinical features

 

 

 

Colour

  • Pale/mottled/ashen/blue

Colour

  • Pallor reported by parent/carer

Colour

  • Normal colour of skin, lips and tongue

Activity

  • No response to social cues
  • Appears ill to a healthcare professional
  • Unable to rouse or if roused does not stay awake
  • Weak, high-pitched or continuous cry

Activity

  • Not responding normally to social cues
  • Wakes only with prolonged stimulation
  • Decreased activity
  • No smile

Activity

  • Responds normally to social cues
  • Content/smiles
  • Stays awake or awakens quickly
  • Strong normal cry/not crying

Respiratory

  • Grunting
  • Tachypnoea:
  • RR > 60 breaths/minute
    Moderate or severe chest indrawing

Respiratory

  • Nasal flaring
  • Tachypnoea:
    RR > 50 breaths/minute
    age 6-12 months
  • RR > 40 breaths /minute
    age > 12 months
  • Oxygen saturation ≤ 93%
    in air

Respiratory

 

Hydration

  • Reduced skin turgor

Hydration

  • Dry mucous membrane
  • Poor feeding in infants
  • CRT ≥ 3 seconds
    Reduced urine output

Hydration

  • Normal skin and eyes
    Moist mucous membranes

Other

  • Age 0-3 months, temperature ≥ 38°C
  • Age 3-6 months, temperature ≥ 39°C
    Bile-stained vomiting

Other

  • Fever for ≥ 5 days
  • A new lump > 2 cm
  • History of rigors
  • Non-blanching rash

Other

  • None of the amber or red symptoms or signs

RED

RED PATHWAY - Enter red pathway if severe infection is suspected, no cause is apparent on examination AND there are either “red features” (Table 2) OR PAWS>10

Table 2. Red clinical features.

Colour

Pale/mottled/ashen/blue

Activity

No response to social cues
Appears ill to a healthcare professional
Unable to rouse or if roused does not stay awake
Weak, high-pitched or continuous cry

Respiratory

Grunting
Tachypnoea: RR > 60 breaths/minute
Moderate or severe chest indrawing

Hydration

Reduced skin turgor

Other

Age 0-3 months, temperature ≥ 38°C
Age 3-6 months, temperature ≥ 39°C
Bile-stained vomiting

1. Does this patient need immediate resuscitation?

? (Paediatric Crash call 2222
Discuss with senior if any uncertainty

Provide high flow Oxygen, assess Airway and Breathing, keep NBM

Cannulate (consider urgency vs use of topical anaesthesia)
If unable to secure access discuss with senior/ consultant
Perform investigations and Treatment as follows

2. Investigations

BM

______

Venous gas:-

pH

______

 

 

 

pCO2

______

 

 

 

HCO3

______

 

 

 

BXS

______

  • BM/ gas satisfactory
    If not Action_________________________

 CRP

 Blood Culture

 FBC

 Urine(consider catheter)

 U&E

  LFT

 Glucose

Ca, Mg

 EDTA blood for PCR (meningo coccalo & pneumo-coccal)

 

 Clotting

 Other________________

 

 

 

3. WARNING - a normal CRP and or FBC does not exclude bacterial infection A negative blood PCR does not exclude N meningitides
4. Be aware of systemic imbalances such as hypoglycaemia, metabolic acidosis, hypokalaemia, hypocalcaemia, hypomagnesaemia, coagulopathy and anamia. These should be highlighted to the Consultant oncall and managed appropriately
5. Commence Treatment

20ml/kg =_____mls / 10minsoFluid bolus 0.9% Sodium Chloride     

6. Empirical Antimicrobials

Check with parents and results server for any previous microbiology results that may affect therapy (e.g. previous MRSA infection)
FOR ALL AGES

If

-status epilepticus

 

-focal seizures

 

-focal neurological signs

 

-encephalopathy

Enter CNS infection in children guideline (Red/ Circle path)

ELSE

 

> 3months of age

Ceftriaxone electronic Medicines Compendium information on Ceftriaxone (80mg/kg) IV single dose - review 24 hours post dose.

   

< 3 months of age

Neonates

 

Benzylpenicillin electronic Medicines Compendium information on Cefotaxime (50mg/kg) IV every 12 hours if <7 days
Benzylpenicillin electronic Medicines Compendium information on Cefotaxime (50mg/kg) IV every 8 hours if ≥7 days
plus
Gentamicin

 

Child 1- 3 months old

 

Cefotaxime electronic Medicines Compendium information on Cefotaxime (50mg/kg) IV every 6 hours

 Assess for signs of shock/ dehydration (resuscitation of children with suspected infection guideline).

If signs of shock persist give further Fluid bolus

20ml/kg=_____mls / 10mins0.9% Sodium Chloride

Re-assess for signs of shock

If signs of shock persist after total 40ml/kg fluid blous
give further
20ml/kg =_____mls / 10minsoFluid bolus 0.9% Sodium Chloride
 discussion with Consultanto
senior / PICU review (MANDATORY)
Inform nursing staff ionotrope infusion likely
Does this patient need a CXR ? (discuss with senior if any uncertainty)
No
Yes. Interpretation________________________________ (pneumonia guideline)
Does this patient need an LP (discuss with senior if any uncertainty)
No
Yes, Counsel parents regarding LP (perform on ward)
Do other specialties need to be made aware of this patient ?
No
Discussed with ______ (grade) __________(specialty) At_____(time)
Arrange admission Requested at___________________
Complete Ward Drug Chart

Time(mins)

0

20

40

60

80

100

120

AVPU rating

 

 

 

 

 

 

 

Resp Rate

 

 

 

 

 

 

 

Pulse

 

 

 

 

 

 

 

BP

 

 

 

 

 

 

 

SaO2

 

 

 

 

 

 

 

Temperature

 

XXXXXXXXXXXXXXXXXXXXXXXXXX

 

If any deterioration in PAWS score, inform Dr immediately


YELLOW

Enter yellow pathway if infection is suspected, no cause is apparent on examination AND there are “yellow features” (Table 2) AND PAWS<10

Colour

  • Pallor reported by parent/carer

Activity

  • Not responding normally to social cues
  • Wakes only with prolonged stimulation
  • Decreased activity
  • No smile

Respiratory
CONSIDER
? CAP guideline

  • Nasal flaring
    Tachypnoea:
    RR > 50 breaths/minute
    age 6-12 months
    RR > 40 breaths /minute
    age > 12 months
  • Oxygen saturation ≤ 93%
    in air

Hydration

  • Dry mucous membrane
  • Poor feeding in infants
  • CRT ≥ 3 seconds
  • Reduced urine output

Other
CONSIDER
?other guideline (osteomyelitis, septic arthritis) more appropriate

  • Fever for ≥ 5 days
  • A new lump > 2 cm
  • History of Rigors
  • Unable to communicate with parents in English

Does this patient need immediate resuscitation?

Discuss with senior if any uncertainty

No

Conscious decision is now made to:
Admit: re-enter RED, Circle pathway

Observe & investigate (without empirical antimicrobial therapy) and Review with observations & results in 2 hours.

Consultant/ Registrar aware

Investigate

Urine (consider catheter)  Blood Culture  FBC  CRP
BMoGas  PCR (meningococcal-, pneumococcal)

Consider other Investigations

CXR (Tempo >39, WCC>20) Interpretation____________________
Other (Malaria,USS)_________

Time(mins)

0

60

120

AVPU rating

 

 

 

Resp Rate

 

 

 

Pulse

 

 

 

BP

 

 

 

SaO2

 

 

 

Temperature

 

 

 

If any deterioration in PAWS score, inform Dr immediately
Results- pay particular significance to neutropaenia (<1.5)

CRP

 

WCC

 

Neutrophil

 

Urine WC

 

Urine RC

 

Urine comment

 

observations & results Discuss with senior to decide

Discharge- enter final common pathway

Else Admit: re-enter RED, Circle pathway

complete investigations in line with RED, Circle pathway
commence treatment in line with RED, Circle pathway
consider need for further investigations


GREEN

If no features of yellow/ red (ie can tick all boxes below) and P

Colour

  • Normal colour of skin, lips and tongue

Activity

  • Responds normally to social cues
  • Content/smiles
  • Stays awake or awakens quickly
  • Strong normal cry/not crying

Hydration

  • Normal skin and eyes
  • Moist mucous membranes

Other

  • None of the amber or red symptoms or signs

Investigate

Observe: Review with observations in 2 hours.

Time(mins)

0

60

120

AVPU rating

 

 

 

Resp Rate

 

 

 

Pulse

 

 

 

BP

 

 

 

SaO2

 

 

 

Temperature

 

 

 

If any deterioration in PAWS score, inform Dr immediately

  • observations satisfactory Discuss with senior if any uncertainty
    Discharge- enter final common pathway
  • Else Admit: re-enter RED, Circle pathway
    complete investigations in line with RED, Circle pathway
    commence treatment in line with RED, Circle pathway
    consider need for further investigations

Other considerations for admission

In addition to the child's clinical condition, consider the following factors when deciding whether to admit a child with fever to hospital:

  • social and family circumstances
  • other illnesses that affect the child or other family members
  • parental anxiety and instinct (based on their knowledge of their child)
  • contacts with other people who have serious infectious diseases
  • recent travel abroad to tropical/subtropical areas, or areas with a high risk of endemic infectious disease
  • when the parent or carer's concern for their child's current illness has caused them to seek healthcare advice repeatedly
  • where the family has experienced a previous serious illness or death due to feverish illness which has increased their anxiety levels

Specific Conditions

  1. Kawasaki's
    Consider Kawasaki disease in children with fever that has lasted longer than 5 days and who have 4 of the following 5 features:
    • bilateral conjunctival injection
    • change in mucous membranes in the upper respiratory tract (for example, injected pharynx, dry cracked lips or strawberry tongue)
    • change in the extremities (for example, oedema, erythema or desquamation)
    • polymorphous rash
    • cervical lymphadenopathy.
      Be aware that, in rare cases, incomplete/atypical Kawasaki disease may be diagnosed with fewer features.
  2. Specific Conditions - see table 2

Final Common Pathway

  • Repeat set of observations satisfactory
  • Job list/ virtual ward list completed
    Name
    d.o.b.
    investigation to chase (eg urine, blood culture)
    telephone contact information entered into job list/ virtual ward
  • Patient advice leaflet given to parents and information for self help groups
  • Discharge letter
    given to parents
    faxed to GP
  • Contact number to CAT given
    Explain parents to use this over next 48hrs

Discharged at time__________

Follow-up. Follow-up for pyrexia of unknown origin depends on final diagnosis and should be discussed with the Consultant. All Children with proven or suspected bacterial meningitis should have a hearing check within 4 weeks arranged and follow-up with the results with Children’s Medicine. Consider additional follow-up with appropriate specialities based on co-morbidities. HV and or school nurse should be informed.

4.6. Children with a second episode of meningitis, meningococcal non group-B serotypes, or who have a history of recurrent bacterial infection should be considered by the consultant for immune testing. In addition those with meningococcal disease with a FH of meningococcal disease or complement deficiency

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Background

Despite advances in healthcare, infections remain the leading cause of death in children under the age of 5 years. Fever is the most common presenting sign of infection in children.

Feverish illness in young children usually indicates an underlying infection and is a cause of concern for parents and carers. Feverish illness is very common in young children, with between 20 and 40% of parents reporting such an illness each year. As a result, fever is probably the commonest reason for a child to be taken to the doctor. Feverish illness is also the second most common reason for a child being admitted to hospital.

Fever in young children can be a diagnostic challenge for healthcare professionals because it is often difficult to identify the cause. In most cases, the illness is due to a self-limiting viral infection. However, fever may also be the presenting feature of serious bacterial infections such as meningitis, bloodstream infection, pneumonia or urinary tract infection. A significant number of children have no obvious cause of fever despite careful assessment. These children with fever without apparent source are of particular concern to healthcare professionals because it is especially difficult to distinguish between simple viral illnesses and life-threatening bacterial infections in this group. Any child with a fever can potentially have a life threatening bacterial infection and the aim of this guideline is to help to reduce the risk of missing a serious infection while also attempting to minimize the risk of unnecessary treatments and admission to hospital.

Microbiology/epidemiology.

The predominant pathogens causing severe infection very with age.
1. Neonates:
Early onset neonatal sepsis, EOS (<48 hours of age) has an incidence of 0.9/1000 live births in the UK. Group B streptococci (50%) and Escherichia coli (18%) are the main causes of early onset neonatal sepsis. Listeria monocytogenes is an uncommon cause of infection in this age group accounting for 6% of cases; in 2010 the Health Protection agency reported 2.3 Listeria cases/1000000 population in the 0-9 years age range (Health Protection unit, Listeria cases: England and Wales by age as rates 1990-2010, accessed 13/09/2011), most of which were early onset neonatal sepsis. Other pathogens causing EOS include: other streptococci (6%), Haemophilus influenzae and Staphylococcus aureus (5%); enterococci, other Enterobacteriaceae (coliforms) and Pseudomonas each account for 1-2%
Late onset neonatal sepsis (LOS) acquired in the community is caused by the same pathogens as EOS, but Listeria monocytogenes very rare. Staphylococciand Gram negative pathogens are more prevalent on neonatal units and premature babies, hence the need for a separate neonatal unit guideline.

For infants younger than 3 months, group B streptococci can be a cause of meningitis and bloodstream infection; from three months to 2 years of age Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus and Haemophilus influenza are key pathogens, while Neisseria meningitidis, Streptococcus pneumonia are more important in children from 2-16 years.

Thus, in a seriously ill child with a fever and suspected bacterial infection antibiotics should be directed against Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus and Haemophilus influenzae. Resistance to penicillin among Neisseria meningitidis and Streptococcus pneumoniae isolates is rare in the UK, but is common in Escherichia coli, Staphylococcus aureus and Haemophilus influenzae. A travel history is important to identify possible acquisition of resistant pathogens as well as less common causes of severe infection such as Plasmodium falciparum malaria.

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Clinical Diagnosis

Recommendation: The management pathway, as shown in the summary, should be determined by a careful history and examination, ensuring the details below are checked and recorded in the medical notes. [Evidence level C]

History
This should include:

  • Onset and course of current illness (including professional assessments and investigations).
  • Medications used and effect upon this illness.
  • Oral intake. Stool/ urine output.
  • Demeanour of child.
  • Past medical history (including previous in-patient admissions for infections, and their duration).
  • Birth history.
  • Recent travel history (previous 1 year).
  • Drug history including: recent antimicrobials; allergies; immunisations.
  • Family history. Contacts with illness (e.g. TB, Varicella Zoster- chickenpox).

Examination
This should include:
Full general examination (Cardiovascular system (CVS), respiratory system (RS), abdomen, Ear/nose/throat (ENT), central nervous system (CNS), skin, soft tissue, bones and joints, regional lymph nodes) to identify a presumptive cause for fever.

If a potential source of infection is identified, this pathway does not apply and the relevant guideline should be followed; This guideline is specifically for a child with no identified cause for their fever.

Ophthalmic and dental examinations should be performed in the absence of any other positive findings and as permitted by the clinical state of the child/ young person.

WARNING - infants may not have the classical symptoms and signs of meningitis.

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Investigation

Recommendation I1: Blood should be tested using BM strip for glucose estimation in children with suspected infection and any RED or YELLOW features. [Evidence level B]

Recommendation I2: Blood cultures should be taken in children with suspected infection and any RED or YELLOW features1. [Evidence level B]

Recommendation I3: Blood should be sent for urea and electrolytes, glucose, liver functions tests, coagulation screen and C-reactive protein in children with suspected infection and any RED or YELLOW features. [Evidence level B]

Recommendation I4: A full blood count should be sent from in children with suspected infection and any RED or YELLOW features. [Evidence level D]

Recommendation I5: Blood should be sent for pneumococcal and meningococcal PCR in children with suspected infection and any RED or YELLOW features. [Evidence level B]

Recommendation I6: A urine sample should be sent for culture whenever possible in all children <3 months with suspected infection of unknown cause. [Evidence level B]

Recommendation I7: A urine sample should be dipsticked in all children >3 months with suspected infection of unknown cause and sent for culture, if positive for leukocytes and/or nitrites. [Evidence level B]

Recommendation I8: A chest x-ray should be requested in children with suspected infection, any respiratory signs or symptoms and any RED or YELLOW features. [Evidence level B]

Recommendation I9: Blood should be sent for malaria investigations in children with suspected infection and travel to a malaria endemic area. [Evidence level B]

Recommendation I10: Medical notes and the results server should be checked for any previous microbiology results (e.g. previous colonization/infection with MRSA) that might affect empirical treatment regimens. [Evidence level D]

Initial investigations have two key functions:

  1. Confirming a diagnosis of infection, identifying the causative organism or providing supportive evidence that there is no infection.
  2. Identifying conditions that present an immediate threat to life (respiratory insufficiency, shock, hypoglycaemia,) permitting immediate treatment.

Blood culture is a vital investigation that is frequently poorly performed; following blood glucose estimation (BM) it is the most essential test. It is advised to take particular notice of the volume of blood required (1-3mls). A full blood count provides a neutrophil count which may support an infective aetiology if the diagnosis of bacterial infection is in doubt, but this is neither reliably sensitive nor specific enough to be relied upon alone. Measurement of renal function is necessary to help guide fluid management and to dose antimicrobials appropriately. C-reactive protein is not sensitive or specific for the diagnosis of bacterial infection but can be useful at baseline to monitor response to therapy and subsequent oral switch or stopping of antimicrobials.

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Treatment
Non-Antimicrobial Treatment

Recommendation: This should proceed as standard Paediatric Life Support (APLS, EPLS, PLS) training. [Evidence level C]

Identifying & treating :-

  • Airway compromise (actual or potential)
  • Respiratory insufficiency
  • Circulatory insufficiency
  • Neurological compromise
  • Metabolic compromise (hypoglycaemia)

One should have a low threshold for securing additional expert assistance Paediatric CRASH 2222

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Empirical Antimicrobial Treatment

Recommendation: Neonates (under 1 month) with suspected severe infection but no clinically obvious focus should be empirically treated with a combination of Benzylpenicillin electronic Medicines Compendium information on Cefotaxime plus Gentamicin, unless there are relevant previous positive microbiology results (e.g. known colonisation with MRSA) which require discussion with microbiology.

Recommendation: In children 1-3 months old with suspected severe infection (red features) but no clinically obvious focus of infection Cefotaxime electronic Medicines Compendium information on Cefotaxime monotherapy unless there are relevant previous positive microbiology results (e.g. known colonisation with MRSA) which require discussion with microbiology [Evidence level C]

Recommendation: In children over 3 months old with a fever and evidence of severe infection (red features) but no clinically obvious focus of infection ceftriaxone is advised 1 [Evidence level C]

Recommendation: Empirical antimicrobial regimens should be reviewed with microbiology results and stopped or amended accordingly. [Evidence level C]

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Directed Antimicrobial Treatment (when microbiology results are known)

Recommendation: Empirical antimicrobial regimens should be reviewed with microbiology results and stopped or amended accordingly. [Evidence level C]

Recommendation: If a specific pathogen or source of infection is identified as a result of clinical assessment, a period of observation or investigations, therapy should be amended appropriately and relevant treatment guidelines/pathways followed. [Evidence level D]

Specific antimicrobial advice regarding directed treatment is outside the scope of this guideline. Many episodes of feverish illness in children are treated as suspected sepsis- awaiting negative microbiological results to safely discontinue empiric antimicrobials. This highlights the importance of blood culture sampling- to permit a decision regarding discontinuing or continuing antimicrobials empirically.

The decision to discontinue antimicrobials is at the discretion of the on-call Consultant, and is usually made 36-48 hours after cultures were taken, in the light of microbiological (culture, PCR) and other investigations (Chest x-ray) and the clinical condition of the child.

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Duration of Treatment

Recommendation: All prescriptions for antibiotics should be reviewed on a daily basis in conjunction with a clinical assessment and results of investigations. [Evidence base C]

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Switch to oral agent(s)
This guideline concerns the initial management of suspected infection, switch to oral agents will depend upon the final clinical diagnosis and consultation with appropriate guidelines is advised.

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Treatment Failure

Recommendation: Treatment failure should be understood as:

  • clinical deterioration (with or without ongoing symptoms)
  • ongoing fever (with no clinical deterioration)

Clinical deterioration should be managed as from the summary of this document, & mandates notification of the on-call consultant.
Ongoing symptoms will be addressed by the on-call consultant at the following ward round.

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Provenance

Record: 2671
Objective:

Aim

  • To improve the diagnosis and management of suspected severe infection of unknown source in children

Objectives

  • To provide evidence-based recommendations for appropriate diagnosis and investigation of suspected sepsis in children
  • To provide evidence-based recommendations for appropriate non-antimicrobial management of suspected severe infection of unknown source in children
  • To provide evidence-based recommendations for appropriate empirical antimicrobial therapy of suspected severe infection of unknown source in children
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To advise in the event of antimicrobial allergy.
  • To set-out criteria for referral to specialists.
Clinical condition:

Sepsis of unknown origin

Target patient group: Children with sepsis of unknown origin
Target professional group(s): Secondary Care Doctors
Adapted from:

Evidence base

References

  1. NICE. Feverish Illness in children: the assessment and initial management in children younger than 5 years: National Institute for Health and Clinical Excellence, 2007. (replaced by CG10 May 2013)
  2. Metsvaht T, Ilmoja ML, Parm U, Maipuu L, Merila M, Lutsar I. Comparison of ampicillin plus gentamicin vs. penicillin plus gentamicin in empiric treatment of neonates at risk of early onset sepsis. Acta Paediatr 2010;99(5):665-72.
  3. Muller-Pebody B, Johnson AP, Heath PT, Gilbert RE, Henderson KL, Sharland M. Empirical treatment of neonatal sepsis: are the current guidelines adequate? Arch Dis Child Fetal Neonatal Ed 2011;96(1):F4-8.
  4. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics 2006;117(1):67-74.

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

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