NIPAH VIRUS INFECTION

• A newly emerging zoonosis 
• RNA virus of the family Paramyxoviridae, genus Henipavirus, and closely related to Hendra virus.
• Gets its name from the village in Malaysia where the person from whom the virus was first isolated succumbed to the disease. 

Spread- 

• Natural host - fruit bats of the Pteropodidae Family, Pteropus genus. (Grey-headed flying foxes - Pteropus poliocephalus)
• The virus is present in bat urine and potentially, bat faeces, saliva, and birthing fluids. 
• Transmission may be due to fomites – or carrying the virus on clothing, equipment, boots, vehicles.

Outbreaks- 

• First outbreak - in Kampung Sungai Nipah, Malaysia, 1998. Intermediate hosts- Pigs. 
• In 2004, Bangladesh - humans became infected with NiV as a result of consuming date palm sap that had been contaminated by infected fruit bats. 
• Human-to-human transmission - documented. 
• Can cause disease in pigs and other domestic animals

Clinical features- 

• incubation period of 5 to 14 days
• Presenting symptoms - 3-14 days of fever and headache, followed by drowsiness, disorientation and mental confusion. 
• Can progress to coma within 24-48 hours.
• Ranges from asymptomatic infection to acute respiratory syndrome and fatal encephalitis. 
• Some patients have a respiratory illness during the early part of their infections, and half of the patients showing severe neurological signs showed also pulmonary signs.
• Long-term sequelae noted -persistent convulsions and personality changes.
• Latent infections with subsequent reactivation of Nipah virus and death have also been reported months and even years after exposure.

Treatment -

• No specific treatment 
• Intensive supportive care 
• No vaccine 

Ref -

WHO 

CDC 

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Burkholderia

Historically, considered  Pseudomonas  species - previously known as  Pseudomonas  multivorans  and  Pseudomonas  kingie.

• Aerobic gram-negative bacteria
• Acquire motility via multitrichous polar flagella.
• Do not ferment glucose 
• Many clinical isolates give a weak oxidase reaction. 
• Slow-growing morphotypes, may go undetected in routine cultures
• Free-livingorganisms present in most aquatic and humid environment, including hospital drinking water. 
• nine  genomovars  grouped  under  “B.  cepacia  complex”  (BCC)
• Burkholderia cenocepacia and Burkholderia multivorans are the prominent bacterial strains isolated from patients with cysticfibrosis.

Infection- 

1.  Lung - 
   

• B. cepacia  gained notoriety as the cause of a rapidly fatal syndrome of respiratory distress and septicemia (the “cepacia syndrome”) in CF patients.
  
• B.  cepacia  regarded  as  important  multi-drug resistant  gram-negative  bacteria  in  the  immunosuppressed  cancer  and transplant  populations.
  
• Nebulizer-associated  BCC  pneumonia  outbreaks  have  occurred  in patients  with  lymphoid  and  myeloid  neoplasms  receiving  aerosolized antimicrobial  prophylaxis
• The risk for  nosocomial  BCC  pneumonia  includes  patients  in  a  critical  care  unit for  longer  than  1  week,  those  requiring  assisted  ventilation,  and  those on  broad-spectrum  antimicrobial  therapy. 
• Hospital  fomites  and  ventilator  humidification  system  may be  potential  sources

      2. Skin,  Skin  Structure,  and  Joint  Infection - 

• Risk  factors - patients receiving  care  in  burn  units  and  those  in  critical  care  units  exposed  to contaminated  disinfectants  or  unsterilized  skin  moisturizing  products.
• Hematogenous  B.  cepacia  dissemination  may  present  as ecthyma  gangrenosum–like  skin  lesions,  particularly  in  patients  with underlying  cancer  or  other  immunosuppression.
• B.  cepacia  septic  arthritis  via  hematogenous  seeding  is  serious,  although  a  rare  complication.

      3. Genitourinary  Tract  Infection - 

• Iatrogenic  infection  from  manipulation  of  the  genitourinary  tract  such as  with  transrectal  prostate  biopsy  and  a  cystoscopy-related  intramural bladder  wall  B.  cepacia  abscess  have  been  rarely  observed.
• In  critical  care  units,  nosocomial  B.  cepacia  genitourinary  tract  infection arises  from  prior  colonization  of  a  urinary  catheter.

Diagnosis-

• Antibiotic-containing  media  can  be  used  to  promote  selective  growth (e.g.,  Pseudomonas  cepacia  agar,  oxidation-fermentation  polymyxin bacitracin  lactose  agar,  and  B.  cepacia  selective  agar).  These  culture media  containing  gentamicin,  polymyxin  B,  and  vancomycin  can  be used  to  isolate  over  90%  of  BCC  within  48  to  72  hours.
• Upto 36% of Burkholderia speciesmay be misidentified by automated systems as other nonfermentativebbacteria,such as Achromobacter or Ralstonia.

Resistance patterns - 

• Drug-resistance  pathways  include  efflux  pumps  (including  adenosine triphosphate–binding  cassette  transporters),  antimicrobial  degradation  and/or  modifying  enzymes,  and  altered  membrane  function.

Rx- 

• Monotherapy not recommended as high chances of failure and infection relapse
• Carbapenems, TMP/SMX, chloramphenicol, and tetracycline
• Susceptible to minocycline(38%), meropenem(26%), and ceftazidime(23%).
• Ceftazidime, tobramycin, and ciprofloxacin retain antimicrobial activity against planktonic and biofilm-embedded organisms.
• Tigecycline  is  less  effective  compared  with  minocycline,  and  overexpression  of  efflux  pumps  may  result  in  development  of  de  novo  drug resistance.
• Combination therapy for serious pulmonary infection (e.g., in CF) is suggested when multidrug-resistant strains are implicated. 
• The combination  of  meropenem  and TMP-SMX  may be antagonistic, however. 

Ref-

Mandell - Principles and practice of Infectious Diseases , 8th edition 

Harrison’s Principles of Internal Medicine, 19th edition 

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Mixed venous oxygen saturation (SvO2) - Pathophysiologic basis

Ref: Functional Hemodynamic monitoring by M.R. Pinsky, D. Payen

As DO2 (Oxygen delivery) is reduced - in critical illness by hypoxemia (hypoxic hypoxia), anemia ( anemic hypoxia), decreased cardiac output (stagnant hypoxia), or any combination thereof - oxygen consumption (VO2) is maintained by virtue of peripheral tissues taking up a greater fraction of the oxygen delivered.

At a sufficiently low level of delivery, approximately 7 ml/kg/min in this example - VO2 becomes dependent on DO2 and further reductions in DO2 are associated with a fall in VO2. This delivery-dependent limb of the VO2-DO2 relationship is characterized by lactic acidosis, organ dysfunction, physiologic instability and death.

As shown in the figure above, SvO2 falls as DO2 is diminished, reflecting tissue uptake being maintained, extraction fraction (VO2/DO2) rising, and arterio-venous content difference widening. SvO2 decreases because oxygen extraction increases. Thus, SvO2 can provide an early signal to determine the adequacy of delivery.

Oxygen extraction fraction (VO2/DO2) is not maximal at the critical delivery point - it continues to increase as DO2 falls below the critical point. However the increase in extraction fraction is not sufficient to maintain VO2, which becomes DO2 supply-dependent.

The rationale for a low SvO2 signalling inadequate DO2 is less clear in pathophysiologic processes associated with high output hypotension - sepsis, liver failure, pancreatitis, and other conditions marked by a systemic inflammatory response syndrome. In these conditions, once fluid resuscitation has taken place, the circulation is characterised by high flow, low systemic arterial pressure, and a high SvO2 despite an elevated oxygen consumption. It is also arguable that tissue hypoxia does not exist under these conditions, or at least is not the primary determinant of lactic acidosis. 

Nonetheless, it has been argued that while a high SvO2 may not guarantee absence of lactic acidosis or a risk for progression of organ failures, a low SvO2 signals inadequate resuscitation and has in fact been used as an endpoint for outcome studies assessing benefit from specific algorithms titrating therapy to this endpoint.

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WHO Guidelines for the Management of Malaria

Recommendations for Parasitological diagnosis:

Recommendation	Level of Evidence
In areas of low to moderate transmission, prompt parasitological confirmation of the diagnosis is recommended before treatment is started.	E
In areas of high stable malaria transmission, children under 5 years should be treated on the basis of clinical diagnosis. In older children and adults including pregnant females, a parasitological diagnosis is recommended before treatment is started	E
In all suspected cases of severe malaria, a parasitological confirmation of the diagnosis of malaria is recommended. In absence or delay in diagnosis, patients should be treated on clinical grounds.	E

 

Treatment of Uncomplicated P. Falciparum Malaria:

To counter the threat of resistance of P. Falciparum to monotherapies, and to improve treatment outcome, combination of antimalarials are now recommended.

Recommendation	Level of evidence
The treatment of choice for uncomplicated falciparum malaria is a combination of two or more antimalarials with different mechanisms of action	S, T, O
Artemisinin-based combination therapies (ACTs) are the recommended treatments for uncomplicated falciparum malaria	S
The following ACTs are currently recommended: Artemether+Lumefantrine, Artesunate+Amodiaquine, Artesunate+Mefloquine,                    Artesunate+Sulfadoxine-pyrimethamine	S, T, O
The choice of ACT in a country or region will be based on the level of resistance of the partner medicine in the combination: - in areas of multidrug resistance (SouthEast Asia), Artesunate+Mefloquine or Artemether+Lumefantrine - in Africa, Artemether+Lumefantrine, Artesunate+Amodiaquine,	E      S
The artemisinin derivative components of the combination must be given for at least 3 days for an optimum effect	S
Artemether+Lumefantrine ahould be used with a 6-dose regimen	T, E
Amodiaquine+Sulfadoxine-Pyrimethamine may be considered as an interim option where ACTs cannot be made available	E

If malaria is suspected and the decision to treat is made, then a full effective treatment is required, whether or not the diagnosis is confirmed by a test.

Recommendations on treatment approaches that should be avoided: 

Recommendation	Level of evidence
Partial treatment should not be given even when the patients are considered to be semi-immune or the diagnosis is uncertain.	E
The Artemisinin and the partner medicines of ACTs should not be available as monotherapies	E

Recommendation for Treatment Failure Management:

Failure within 14 days:

- Must be confirmed Parasitologically

- Should be treated with second line drugs

Failure after 14 days:

- Can be treated with the first line ACTs, except when initially treated with Mefloquine.

- Parasitological confirmation is desirable, but not a pre-condition.

Recommended Second-line antimalarial treatments:

- Alternative ACT known to be effective in the region

- Artesunate + Doxycycline/ Tetracycline/ Clindamycin

- Quinine + Doxycycline/ Tetracycline/ Clindamycin

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