Category Archives: Infectious disease

Uveitis

The Uvea is the term for the whole eye (uvea=peeled grape). Whereas conjunctivitis looks like a red eye, it’s only really the surface that is inflamed. With uveitis, all the different tissues of the eye are inflamed. Acutely, might not look that different to conjunctivitis but painful, whereas latter usually just itchy. Anterior chamber starts to fill up with inflammatory cells so vision starts to deteriorate. An irregular pupil due to synechiae can eventually be seen, with hypopyon. Cataracts and scarring can follow.

Chronic on the other hand can be subclinical but potential for visual loss so screening important in associated conditions.

Usually idiopathic, otherwise:

  • Juvenile idiopathic arthritis – about 10% of patients with non-oligoarthritis, and 30% of ANA positive oligo so pretty common
  • HLA-B27 – with or without other B27 conditions such as Ankylosing spondylitis
  • Behcet’s disease (so do HLA B51)
  • Crohns disease and other IBD
  • Granulomatosis with polyangitis (ex-Wegeners)
  • Sarcoidosis (so do chitotriosidase)
  • Tubulointerstitial nephritis and uveitis (TINU) syndrome

Some infections can cause it:

Quinolones

eg ciprofloxacin.

Broad spectrum antibiotics.

Block DNA synthesis by bacteria (uniquely among antibiotics).

Good against gram negatives, including Salmonella, Shigella, Neisseria, Pseudomonas (one of the few oral antipseudomonals).

Good intracellular penetration so active against organisms such as Chlamydia, Mycoplasma, Legionella and some Mycobacteria.

Good tissue penetration including central nervous system. 80% of orally administered drug is bioavailable so the IV route is only used when absorption impaired.

But no anti-anaerobic activity, and not very good against common gram positives eg Pneumococcus, Enterococcus, Staphylococcus (in fact, use is associated with MRSA). The newer types (Gatifloxacin, Moxifloxacin, Levofloxacin) have better gram positive activity but would still not be your first line choice, and have less anti-pseudomonal activity.

Not licensed under 1yr.

Only contraindication is previous tendon problem caused by it!

Adverse Effects:

  • Disabling, long-lasting (even irreversible) musculoskeletal and neurological problems reported, v rarely. So only use for severe infections, unless no other antibiotic appropriate. And stop ASAP if symptoms (muscle pain, joint pain, weakness, neuropathy etc)
  • Seizures (+/- predisposing condition)
  • Tendonitis – rupture can occur within 48hrs of starting, but can also be months later! Steroids at same time may increase risk, as may renal impairment and solid organ transplants
  • Arthropathy in immature animals – so avoided in children (except Nalidixic acid) unless extenuating circumstances (only reversible musculoskeletal symptoms have been reported). Arthropathy occurs in CF anyway.
  • Can prolong QT
  • Photosensitivity
  • Valve regurgitation – so caution if preceding valve disease or other risk factor eg connective tissue disorder (Ehlers-Danlos, Marfans), hypertension (!), Turners (!)

SARS-CoV-2 vaccine

Multiple vaccines in the pipeline, mostly against spike (S) protein in SARS-CoV-2 that facilitates host cell entry.

Pfizer vaccine is mRNA vaccine, completely in vitro derived, uses nanoparticles to aide absorption into host cells which then produce the S protein themselves from the mRNA. AstraZeneca vaccine is chimp adenovirus vector for genetic sequence – mRNA produced once virus taken up by host cell.

Single dose IM injection.

Staphylococcal bacteraemia

7-14 days IV recommended if uncomplicated. Higher relapse rate with shorter course.

Uncomplicated viz

  • Negative repeat blood cultures
  • Defervescence within 72 hours of treatment
  • No evidence of endocarditis
  • No prosthesis or venous catheter
  • No evidence of metastatic infection

I wonder about PVL positive though.

Should echo if high risk for endocarditis or persistent fever.

Consider removing catheters

Neonates should get 14 days IV.

If endocarditis, then 4-6 weeks IV treatment.

If osteoarthritis, then 3-6 weeks IV/oral treatment.

[Peds 2020]

Hyper IgE Syndrome

This is a rare, autosomal dominant (sporadic) immunodeficiency characterized by:

  • recurrent staphylococcal skin infections (cold abscesses)
  • lung infections causing pneumatocoeles, which then invite aspergillomas
  • mucocutaneous candidiasis
  • eczema, eosinophilia and high IgE

PLUS bony abnormalities:

  • osteopenia and spontaneous bone fractures
  • dysmorphism: triangular jaw, wide nose, asymmetrical face
  • dental abnormalities eg retained primary
  • hyperflexibility and scoliosis

Also called Job’s (because of the Bible story, smitten by boils etc, but could equally have been CGD!) or Buckley syndrome.

Caused by STAT3 defect, part of IL6 receptor. Not an immunoglobulin problem but if antibiotic prophylaxis is ineffective, IVIG is sometimes used.

An autosomal recessive form without the bone abnormalities but with vasculitis esp CNS involvement described.

SARS

Severe acute respiratory syndrome – caused by one of the coronavirus group, see also MERS and COVID19. The virus probably originated in bats, then crossed into humans via masked palm civets.

The virus spread beyond its original outbreak in China when a businessman became unwell on his flight out of China and died in Vietnam in 2003. Further outbreaks appeared rapidly, as far afield as Toronto. Eventually led to 8000 cases globally, but rapid surveillance and isolation measured brought the epidemic to an abrupt end within 4 months.

Super shedders exist, who have much higher infectivity (1 case on a plane infected 120 others, whereas another plane had 4 cases on board, but no secondary cases occurred!). On the other hand, there is no documented transmission by asymptomatic cases, or between children.

Incubation period is 5-7 but up to 14 days. Spread is by respiratory, fomites, and faecal-oral routes. Peak shedding occurs at peak of clinical disease hence outbreaks were often among health care workers.

Symptoms are ‘flu-like, and non-specific. Fever is universal. Those who do badly have sudden deterioration on 10th day, with ARDS. Mortality is around 10%, but very age dependent, reaching over 50% in the over 65s. Children have lower viral loads, and generally have a benign course. Compared with adults, they perhaps get more gastrointestinal symptoms than respiratory.

Children under 5 yrs are hardly affected at all – perhaps because recent coronavirus infection protective, perhaps because of reduced immune reactivity.

No long term morbidity seen in children.

The diagnosis is suggested by the paucity of clinical signs (mild crepitations only, if anything) with an abnormal chest radiograph (non-specific), and laboratory evidence of leucopenia, lymphopenia, and thrombocytopenia. Raised AST/ALT also seen.

Definitive diagnosis is by ELISA or PCR, neither of which is very sensitive, or useful early on in disease.

Interferon alpha appears to be of benefit in vitro. Otherwise supportive.

Personal Protective Equipment effective if used properly – so buddy system.

Infection control – encourage self isolation, dedicated staff etc.

MERS

Middle East respiratory syndrome, caused by a coronavirus
(MERS-CoV) . See also COVID19 and SARS.

Reported 2012.  More than 2000 cases so far, mostly related to Arabian peninsula, but a single case of MERS-CoV in a returning traveller led to an outbreak involving 186 cases across 16 hospitals in the Republic of Korea.

36% mortality, mostly people with co-morbidities. More than 2000 cases so far. 

One of WHO blueprint priority diseases – potential for serious outbreak, no treatment or vaccine (6-7 others: SARS, Crimean-Congo HF, Ebola, Lassa etc).

Incubation time 2-5 days but up to 14. Median onset to hospitalisation 4 days.

Risk factor appears to be camel contact – milk, meat, urine.

Management

Management based on experience of SARS etc.

Infection control – negative pressure, dedicated staff, cleaning, PPE for suspected cases, self isolation for close contacts. 

COVID19

Hogmanay 2019 WHO were informed of cluster of cases of Pneumonia of unknown cause in Wuhan city, Hubei province, China.

Novel coronavirus identified, named SARS-CoV-2. COVID19 is associated disease. Similar viruses responsible for SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).

By end of February 2020, more than 70 000 cases reported across China, 2500 fatalities. Pandemic was declared by WHO on 11th March.

Cruise ships including the Diamond Princess in Japan (over 700 cases) and the Zaandaam were particularly hard hit.

Lockdown declared in UK on 23rd March.

Binds to ACE2 – potentially explaining particular susceptibility among people with hypertension and Africans (nearly double rate of whites) and Asians (although Indian rates lower than Bangladeshi/Pakistani). Rates among Chinese females actually lower than among Whites! [uk data]

Risk of “critical illness “ from COVID-19 RR 1.44 if overweight, 1.97 if obese. UK OpenSAFELY analysis. Death 1.27 if BMI 30-39, 2.27 if BMI>40. ACE-2 higher in obese. Plus different immune responses and challenges to ventilate.

London has double the age standardised mortality of any other part of the UK (Birmingham next), as high as 144 per 100 000 in Newham. Glasgow’s rate is about 80 [UK data]

Bronx worse hit than Manhattan, despite similar population density. Higher attack and death rates among Afro-Americans. Role for air pollution too?

Plot of mortality rates by gender/race

Some reports of acute neurological presentations in adults, including stroke and Guillain Barre syndrome.

Transmission potential of asymptomatic cases (common on cruise ships) yet to be determined.

See Treatment.

COVID in Children

Probably more severe than SARS but still children tend to be less severely affected than adults. Cross protection from immunity from other coronaviruses? Differences in ACE2? Some asymptomatic.

Wheeze uncommon. Asthma does not appear to increase risk (in China).

X-ray more often negative; CT more sensitive.

Can present with GI symptoms.

One baby born to an infected mother developed severe complications.

Neutrophil and LDH counts go up, lymphocytes go down.

A small series of children with COVID-19 has shown a greater prevalence of peripheral halo (halo-sign) lung consolidations on CT.

The criteria for the definition of Acute Respiratory Distress Syndrome (ARDS) and septic shock, the guidelines for the management of sepsis and septic shock and the use of non-invasive ventilation in children are different from those of adults.

Children desaturate more easily during intubation; therefore, it is important to pre-oxygenate with 100% O2 with a mask with a reservoir before intubating.

A rectal swab may be useful in children to determine the timing of the termination of quarantine.

[Chengdu and Italian experience, from PIPSQC]

WHO supports use of dexamethasone in patients with acute respiratory presentation and hypoxia (sats<90%), tachypnoea, or severe respiratory distress. RECOVERY trial continues to study dexamethasone in neonates, plus roles for azithromycin and toculizimab.

Remdesivir is licensed in hospitalised patients in oxygen, over 12 years and over 40kg and can be considered in this age group for patients with high-risk comorbidity,

Paediatric multi inflammatory syndrome associated with COVID19 (PIMS-TS)

Neutrophilia (most), lymphopenia, single or multiorgan dysfunction.  Possibly Kawasaki criteria. Exclude other infectious cause including shock syndromes and myocarditis (but don’t delay seeking advice).

Abnormal fibrinogen, d-dimer, ferritin, hypoalbuminaemia. Other features eg coagulopathy variable.

WHO refer to PIMS-TS as Multisystem Inflammatory Syndrome in Children (MIS-C), case definition is similar but requires at least 3 days of fever and either evidence of COVID-19 on PCR or serology or a likely contact with COVID-19.

Length of PICU stay generally short, some require ECMO, majority survive.

BCG complications

Disseminated BCG reported, implies SCID or similar major immunodeficiency.

Severe BCG reaction can also indicate underlying TB infection!

More common issues are BCG abscess, and lymphadenitis.

Abscess at injection site appears after a few weeks, can persist for months. Treatment with isoniazid has been offered but no evidence of benefit. Incision probably makes things worse!

Non-suppurative lymphadenitis (not tender, no systemic symptoms) improves over a period of few weeks. Can progress to abscess however, with eventual spontaneous discharge and sinus formation. Healing then takes several months. Drug treatment does not appear to prevent abscess formation or speed up healing.

If an axillary abscess develops, needle aspiration can prevent perforation and sinus formation. Surgical excision might be needed if matted or multiloculated.

[ Postgrad Med J 2002;78:327–329]