The Hajj Pillgrimage

The yearly "Hajj" Pilgrimage hosted by the KSA is the "Fifth Pillar of Islam" and is mandatory once in a lifetime for all adult Muslim who are physically and financially able. The Hajj is one of the world's largest annual mass gatherings.1

1.3 Mn

Muslims participate every year1

180+

Countries

500k

Domestic Hajj Pilgrims1

5-6M 

Perform Umrah each year1

Health concerns during Hajj

The Hajj and its rituals are physically demanding for Hajj pilgrims, the majority of whom are elderly, with chronic conditions. Although the Hajj rituals only take one week, pilgrims usually stay in the KS for several weeks throughout the month-long Hajj season, presenting a major public health and infection control concern. In addition to physical exhaustion, sleep deprivation (3), and heat stress, inevitable overcrowding, greatly increases the risk of acquiring and spreading infectious diseases especially respiratory diseases.1

Infections during Hajj Pilgrimage

Infections are the first cause of hospital admissions during Hajj, due to the limited time and confined geographical area and the large number of people (7 persons/m2),2,3 Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj.2

Causes of hospitalization in 808 patients during the 2003 Hajj (2,012,074 pilgrims)
Admitting n (%)
Infections 292 (36%)
Cardiovascular diseases 201 (25%)
Pulmunary diseases 109 (14%)
Surgical diseases 98 (12%)
Endocrine diseases 75 (9%)
Gastrointestinal diseases 34 (5%)
Obstetric and gynecological diseases 33 (4%)
Heart-related diseases 32 (4%)
Renal diseases 19 (2%)
Psychiatric diseases 6 (1%)
Other diseases 6 (1%)

Overcrowding

Different Nationalities

High Temperatures

Coincidence with Flu session

Barefoot Walk

Communal Toilets

Respiratory tract infections during Hajj

Respiratory tract infections is a common illness during Hajj. It has been estimated that 1 in 3 pilgrims will experience respiratory symptoms, which usually start at the end of, or shortly after the end of, the Haj season.4

 

41 - 60.8%
Respiratory diseases are the most common cause of outpatient visit2

URTIs
In the ENT clinic alone,
URTIs including pharyngitis, viral URTI,
and tonsillitis, represents 85.2% of the total diagnoses

LRTIs
Pneumonia was confirmed
in 53.9% of pilgrims, 94% of whom
were aged > 50 years

Comorbidity is one of the risk factors for development of RTI. In pilgrims who suffered from comorbidity, there was a significant association with longer duration of cough (P = 0.041), longer duration of sore throat (P = 0.048).3

Cough

Sputum Production

Sore throat

Hoarseness

Rhinorrhea

Fever

Malaise

Cough may persist for several weeks;
and if it is accompanied by purulent
sputum, it suggests the possibility of a
bacterial infection.4

Pneumonia is one of the leading causes of hospitalization of pilgrims in Mecca, especially among elderly people, accounting for 27.2% of all ICU admissions.3

Common Bacterial pathogens during Hajj5

35.3% of the pilgrims acquired at least one following respiratory pathogens after the Hajj,

H. infuenzae

K. pneumoniae

S. pneumoniae

S. aureus

Streptococcus pneumonia is one of the most important causes of morbidity and mortality in CAP

Possible Pneumonia Complications

Sepsis3

Pleurisy3

Lung abscess3

Choice of proper antibiotic therapy is critical to help pilgrims enjoy this spiritual journey.

Burden of anti-microbial resistance during Hajj

The emergence of antimicrobial resistant (AM) bacteria is of worldwide concern and the Hajj poses a serious risk to its dissemination. Recently, a number of studies have highlighted Hajj as a focal point for the emergence and dissemination of AM globally.7,8

The number of common AMR isolates, reported from 1990 to 2021, during the Hajj
Organisms Aminoglycosides

ß-lactams

Macrolides

Quinolones

Sulphonamides

Escherichia coli

 489 726 18 407 426

Enterococcus spp.

 68 176 56 39 21

Klebsiella spp.

 339 475 0 264 242

Proteus spp.

 51 74 0 45 29

Pseudomonas spp

 736 800 0 397 240

H. influenzae

 38 47 0 15 38

Staphylococcus spp.

 621 1748 818 57 696

Streptococcus spp.

 113 146 266 43 380

MRSA incidence was 2-7% in pilgrims in
2000-2004, 28% in patients with sinusitis
in 2014 and 63% in community acquired
infections in 2015

A broad spectrum, appropriate antibiotic with favorable pharmacokinetics
could help prevent development of further AMR

Guideline Recommendations

Quinolones are the recommended treatment options for the management of various infections including ABRS, CAP, HAP and VAP

According to AAO-HNS Guidelines Update 2015

For penicillin-allergic patients, Levofloxacin is one of the recommended agents as an alternative for empiric anti-microbial therapy.10

Antibiotic therapy for acute bacterial rhinosinusitis initial treatment failures.

Patients who were initially treated with amoxicillin without clavulanate can be treated with levofloxacin.10

According to IDSA Guidelines 2012, for adults with a history
of Penicillin Allergy include:

A respiratory fluoroquinolone (Levofloxacin or moxifloxacin) is recommended as an alternative agent for
empiric antimicrobial therapy​​​​​​​ in adults who are allergic to penicillin (strong, moderate)11​​​​​​​

NICE guidelines in moderate to severe CAP management

According to NICE guidelines 2019. For antibiotic comparisons in adults with moderate-or high-severity community
acquired pneumonia, some differences were seen in some efficacy outcomes:

A fluoroquinolone (Levofloxacin or moxifloxacin) compared with a beta-lactam antibiotic plus macrolide: there were no significant
differences in mortality or microbiological failure, but clinical failure was significantly reduced with a fluoroquinolone12

Why Levofloxacin?

Levofloxacin exhibits broad-spectrum bactericidal activity, excellent oral bioavailability, good tissue penetration and favorable safety and tolerability profiles.13-27

    Levofloxacin exhibits broad spectrum activity against susceptible & difficult to treat pathogens and has maintained its efficacy with generally very low rates of resistance, 14-18

    Susceptibility of Gram-negative pathogens to levofloxacin and ciprofloxacin (Trust 10, 2005-2006)19
    Pathogen Levofloxacin

    Escherichia coli

    		 87.8%

    Klebsiella pneumonia

    		 95.7%

    Enterobacter cloacae

    		 93.5%

    Proteus mirabilis

    		 85.5%

    Serratia marcescens

    		 95.6%

    Pseudomonas aeruginosa

    		 69.1%

    Levofloxacin is as effective as combination therapy with a beta lactam and a macrolide for the treatment of patients with CAP requiring hospital admission,25

    Comparative adverse events and discontinuation rates (%) for selected fluoroquinolones

    Events (%)

    Levofloxacin

    Moxifloxacin

    Gemifloxacin

    Gastrointestinal effects

    		      

    Nausea

    		 1.0 7.2 2.7

    Vomiting

    		 0.2 1.0 - 2.0 0.9

    Diarrhea

    		 1.0 5.7 - 8 3.6

    Abdominal pain

    		 0.3 2.0 0.9

    CNS effects

    		      

    Dizziness

    		 0.3 3.0 0.8

    Headache

    		 0.1 2.0 - 8.0 1.2

    Dermatologic effects

    		 0.3 >0.1 - <2.0 2.8

    Discontinuation rate

    		 1.3 - 3.7 2.0 - 5.0 2.2

Benefits of Levofloxacin

HIGH CLINICAL SUCCESS RATE
- AECB - ABS - CUTIs - CAP - SSSIs - Prostatitis
BROAD SPECTRUM
- Gram positive - Gram negative - Atypical pathogens
FAVORABLE PK/PD PROFILE
- Good tissue diffusion - Can be administered without regard to food - 99% bioavailability
- Sequential Therapy (oral IV)
CONVENIENT
- Once-daily dosing
BETTER SAFETY PROFILE
    1. Benkouiten S, Al-Taw_q JA, Memish ZA, Albarrak A, Gautret P. Clinical respiratory infections and pneumonia during the Hajj pilgrimage: A systematic review. Travel medicine and infectious disease. 2019 Mar 1;28:15-26.
    2. Salmon-Rousseau A, Piednoir E, Cattoir V, de La Blanchardiere A. Hajj-associated infections. Medecine et maladies infectieuses. 2016 Oct 1;46(7):346-54.
    3. Aldossari M, Aljoudi A, Celentano D. Health issues in the Hajj pilgrimage: a literature review. East Mediterr Health J. 2019 Oct 1;25(10):744-53.
    4. Alzeer AH. Respiratory tract infection during Hajj. Annals of thoracic medicine. 2009 Apr;4(2):50.
    5. Hoang VT, Ali-Salem S, Belhouchat K, Meftah M, Sow D, Dao TL, Ly TD, Drali T, Ninove L, Yezli S, Alotaibi B. Respiratory tract infections among French Hajj pilgrims from 2014 to 2017. Scienti_c reports. 2019 Nov 28;9(1):1-8.
    6. Pneumonia complications. NHS. Available at https://www.nhs.uk/conditions/pneumonia/ (Last accessed Mar 2020)
    7. Alreeme S, Bokhary H, Craig AT. Transmission of Antimicrobial Resistant Bacteria at the Hajj: A Scoping Review. International Journal of Environmental Research and Public Health. 2022 Oct 29;19(21):14134.
    8. Bokhary H, Barasheed O, Othman HB, Saha B, Rashid H, Hill-Cawthorne GA, Abd El Ghany M, Hajj Research Team. Evaluation of the rate, pattern and appropriateness of antibiotic prescription in a cohort of pilgrims su_ering from upper respiratory tract infection during the 2018 Hajj season. Access Microbiology. 2022;4(4).
    9. Al-Taw_q JA, Memish ZA. The emergence, persistence, and dissemination of antimicrobial-resistant bacteria in environmental Hajj settings and implications for public health. Tropical Medicine and Infectious Disease. 2021 Mar 10;6(1):33.
    10. Rosen_eld R.M., Piccirillo J.F., Chandrasekhar S.S. Brook I, Kumar K.A, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngology – head and Neck Surgery. 2015; 152 (2_suppl): S1-39.
    11. Chow A.W., Benninger M.S., et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clinical Infectious Diseases. 54(8):e72-112.
    12. NICE guideline 2019. Pneumonia (community-acquired): antimicrobial prescribing.
    13. International Journal of Antimicrobial Agents 28S (2006) S115-S127. 3. LEVAQUIN Prescribing Information. September 2008.
    14. CDC. Antibiotic/Antimicrobial Resistance. About Antimicrobial Resistance. 2013 available at: http://www. cdc. gov/drug resistance/about. html. last accessed: 25.8.2015.
    15. Karlowsky JA, Thornsberry C, Jones ME, et al. Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002). Clin Infect Dis 2003; 36 (8): 963-70.
    16. CDC. ABCs Report: Streptococcus pneumoniae, 2003. Available at: http://www.cdc.gov/abcs/reports-_ndings/survreports/spneu03.html. Last accessed: 13.9.015.
    17. Jones RN, Sader HS, Mendes RE, Flamm RK. Update on antimicrobial susceptibility trends among Streptococcus pneumoniae in the United States: report of cettaroline activity from the SENTRY Antimicrobial Surveillance Program (1998-2011 ). Diagn Microbiof Infect Dis 2013; 75(1 ): 107-9.
    18. Farrell DJ, Jenkins SG, Brown SD, Patel M, Lavin BS, Klugman KP. Emergence and spread of Streptococcus pneumoniae with erm(B) and mef(A) resistance. Emerg Infect Dis 2005; 11 (6):851-8.
    19. Z.A. Memish, et al. International Journal of Antimicrobial Agents 23 2004; 32-38.
    20. Tavanic Product monograph. June 2003.
    21. Clin Microbiol Infect 2005; 11 (Suppl. 2): 653, Abs:R 1965.
    22. H.V. Baum, UM 18 (2001); 335-340.
    23. J chemotherapy, Vol 16-supllement n.2 (18-21) 2004 K.G.Naber.
    24. Kohlho_ SA, Roblin PM, Reznik T, Hawser S, Islam K, Hammerschlag MR. In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae. Antimicrob Agents Chemother. 2004 May; 48 (5): 1885-6.
    25. International Journal of Antimicrobial Agents 28S 2006; S115-S127
    26. FDA approval of Levo_oxacin. September 2008.
    27. Clinical infectious disease 1999; 28: 352-64.
    28. Using Safety Pro_les to Di_erentiate between the Newer Fluoroquinolones Keith A. Rodvold. 2007: 23-30.

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