Journal of Infection (1998) 36, 303-306

Tuberculosis is the Commonest Cause of Pneumonia Requiring Hospitalization During Hajj (Pilgrimage to Makkah)

A. Alzeer .1, A. Mashlah 2, N. Fakim 3, N. AI-Sugair a, M. AI-Hedaithy 1, S. AI-Majed 1 and G. Jamjoom ~

1Department of Medicine, 4Department of Microbiology, King Saud University, Riyadh, 2King Abdulaziz Hospital, Makkah, 3A1-Noor Specialist Hospital, Makkah, SChest Hospital, Taif, Saudi Arabia

The diagnosis and treatment of pneumonia in mass gathering situations is a medical challenge, requiring prompt decision making and knowledge of the aetiology.

We studied cases of pneumonia admitted to two hospitals during the 1994 pilgrimage (Hail) season to Makkah. Sixty-four patients were enrolled in the study, of which 47 (75%) were men with a mean age of 63 years (range 21-91). Nearly all were from developing countries. Diagnosis was established in 46 patients (72%) with Mgcobacterium tuberculosis being the commonest causative organism (20%), followed by Gram-negative bacilli (18.8%). Streptococcus pneumoniae accounted for only 10%, with Legionella pneumophilia, Mycoplasma pneu- moniae, and viruses accounting each for 6%. The main finding of this study is that M. tuberculosis is a common cause of pneumonia under these unusual "extreme circumstances". Its presentation was acute and indistinguishable from pyogenic pneumonia. Thirty-one per cent of tuberculous cases had upper lobe involvement, 54% lower lobe, and 15% multi-lobar. This was similar to the radiographic features in non-tuberculous pneumonia cases. All but one patient with tuberculosis recovered following the administration of first-line anti-tuberculous drugs. The total mortality was 17%.

The preponderance of M. tuberculosis and Gram-negative bacteria over S. pneumoniae may reflect the prior use of amoxyciflin and the effect of exhaustion, malnutrition, and old age.

Introduction

The causative organisms and clinical picture of com- muni ty-acquired pneumonia under normal social cir- cumstances are well defined. A few case reports and studies have suggested that pneumonia has a different picture and aetiology under wha t was called "extreme circumstances ''1 in "disaster regions ''2 and camps in de- veloping countries. 2' 3 The combinat ion of overcrowding, exhaustion, and poverty has resulted in a high incidence of pneumonia generally, and in particular, outbreaks of Mycoplasma pneumonia< and a "caseous" form of pul- m o n a r y tuberculosis characterized by severe systemic effects and high mycobacterial load. 1

Pilgrimage to Mald¢ah in Arabia is a unique phe- n o m e n o n with impor tant medical and epidemiological implications which could serve as a model for a setting of "extreme circumstances". Millions of pilgrims, mostly elderly subjects from poor countries with a high pre- valence of infectious diseases like tuberculosis, 4 follow air

* Address all correspondence to: A. Alzeer, Consultant Pulmonologist & Intensivist, Department of Medicine (38), College of Medicine, King Saud University, P.O. Box 18321, Riyadh 11415, Saudi Arabia. Accepted for publication 25 September 1997.

travel by gather ing under crowded conditions (mostly tents) to perform physically-exhausting religious rites. The pilgrimage usually lasts for a few weeks. Al though heat stroke in association with adult respiratory distress syndrome and disseminated intravascular coagulopathy are the best described complications of pilgrimage, s a few reports and anecdotal evidence point to a high incidence of meningitis 6 and respiratory tract infection complicated by high mortality. We decided, therefore, to conduct a study to determine the aetiology, clinical features and outcome of severe pneumonia requiring hospital ad- mission a m o n g pilgrims to Makkah.

Materials and Methods

This cross-sectional study was carried out in two main referral hospitals in the Makkah area (A1-Noor Specialist Hospital and King Abdulaziz Hospital) during the whole of the pilgrimage season, extending between 3 and 28 May 1994. All pilgrims admitted to hospital with pneu- monia were included. Nearly all were referred from hajj camps.

For the purpose of the study, pneumonia was defined as an acute episode associated with respiratory symptoms

0163-4453/98/030303 + 04 $12.00/0 © 1998 The British Infection Society

304 A. Alzeer et al,

and radiological evidence of airspace disease of less than 4 weeks' duration. 7 All patients were examined by a pulmonary physician on entry to the study and the initial diagnosis confirmed. Patients were excluded when pneumonia was not the main reason for hospital ad- mission (such as after t rauma, a stroke, or renal or hepatic failure), if it was an expected terminal event, or pulmonary embolism was suspected. Clinical details including duration of illness, presenting symptoms, co- morbid disease and smoking history were recorded through an interpreter in most of the patients. Haemato- logical and biochemical investigations including total haemoglobin, white blood cell (WBC) count, serum elec- trolytes, glucose, urea and creatinine were measured on admission.

Expectorated sputum was obtained for microscopy and culture. Microscopic examination included immediate Gram and Ziel-Neelsen stains. Only those specimens that had more than 25 WBC and less than 10 squamous epithelial cells per low power field were processed further. Routine laboratory methods were used for culture and identification of micro-organisms. Antimicrobial sus- ceptibility was performed by Stoke's comparative disc diffusion method. 8 Fibreoptic bronchoscopy was done on 28 patients who were considered to have an inadequate sputum specimen and broncho-alveolar lavage (BAL) of the affected segment or lobe was performed. This speci- men was processed in the same way as the sputum. All specimens were also cultured for M. tuberculosis and fungi. Testing for Human Immunodeficiency Virus (HIV) was performed on all the patients by using Vironostika HIV Uni-Form II plus 0 which is an enzyme-linked im- munosorbent assay (ELISA). Specific IgG and [gM anti- bodies tests for Mycoplasma were performed on admission and then repeated 10 -20 days thereafter, and for Le- gionella serology the Zeus Scientific Inc. indirect fluor- escent antibodies (IFA) method was used. Mycoplasma infection was diagnosed by a four-fold rise in IgG antibody titre or presence of IgM positivity, and Legionella infection if serology was positive to a titre of 1:256. Direct im- munofluorescent staining for influenza A, influenza B, para-influenza 1,2,3, adenoviruses and respiratory syn- cytial virus antigens in BAL fluid or naso-tracheal aspirate using reagents from DaKo (Imagen) and Sanofi (Pasteur Diagnostics, France) was performed. The relationship of pathogenic micro-organisms to the pneumonia was modified from those used in the British Thoracic Society studyg: (a) definite: a positive blood culture, M. tuberculosis on culture, positive serology for Mycoplasma or Legionella or direct detection of a virus; (b) probable: a single pathogen in heavy growth from sputum culture; (c) non- diagnostic: a light growth of a single pathogen, mixed growth or no growth.

Table I. Admission details.

No. of patients % n = 6 4

Smokers 17 26.6 Ex-smokers 19 29.7 Chronic obstructive lung disease 23 35.9 Cough 59 92.2 Sputum 42 65.6 Shortness of breath 51 79.7 Chest pain 26 40.6 Haemoptysis 17 26.6 Confusion 36 56.3 Fever 58 90.6

Table II. Cause of pneumonia.

Micro-organism Diagnosis Total (%)

Definite Probable

M. tuberculosis 13 0 13 (20.3) S. pneumoniae 3 3 6 (9.4) Coliforms* 0 7 7 (10.9) L, pneumoniae 4 0 4 (6.3) M. pneumoniae 4 0 4 (6.3) Viruses1- 4 0 4 (6.3) 1t. influenzae 0 3 3 (4.7) P. aeruginosa 1 1 2 (3.1) S. aureus 1 1 2 (3.1) Candida spp. 1 0 1 (1.6) Not diagnosed - - 18 (2 8)

* K. pneumoniae 5, E. coli 1, Serratia spp. 1. 1" Influenza A = 2; influenza B = 1; parainfluenza 3 = 1.

The data was analysed using the Stat Pac Gold Stat- istical Analysis Package. Testing procedures used to detect significant differences between specified groups were Stu- dent's t-test for independent continuous variables. P<O.05 was considered statistically significant.

Results

Sixty-four cases of pneumonia in pilgrims were admitted, 47 (75%) of whom were male. The age ranged between 21 and 91 years, with a mean of 63 ± 11.9 years. Thirty- four per cent came from the Middle East, 31% from South-East Asia, 23% from the Indian sub-continent and 11% from Africa. Chronic obstructive lung disease (COLD) was diagnosed in 23 patients (35.9%). Ten patients (15.6%) with severe pneumonia required mechanical ventilation. The clinical details of the cases are shown in Table I. A total of 41 patients (64.1%) had leucocytosis of more than 10.0 x 109/1 and hypoalbuminemia (<34 g/ I) was present in 28 patients (44.2%). Severe hypoxaemia on air (PO2 <60 mmHg) was present in 27 cases (43.7%)

Pneumonia Causing Hospitalization During Hajj 305

Table lie Comparison between tuberculous and non-tuberculous patients.

Parameters Tuberculosis Non-tuberculosis P- compared patients w i th patients with value

pneumonia pneumonia n=13 n=51

Age 59.3 +_ 14.3 63.8 ± 11.2 0.2 Duration of illness 12.7 _+ 5.5 11.9 _+ 7.2 0.3

(days) WBC x 109/1 14.7 _+ 1.2 15.9 + 8.1 0.2 Glucose mmoI/1 9.4 _+ 8.0 10.0 _+ 6.4 0.4 Urea mmol/1 7.4 _+ 2.7 8.9 ± 5.8 O. 1 Creatinine #mmol/I 86.3 -t- 17.3 114.5 _+ 67.4 0.01 Albumin g/l 36.1 -t- 5.0 32.3 _+ 5.5 0.2 pH 7.4_+0.9 7.4_+0.1 0.5 POx mm Hg 66.0 + 17.0 63.8 _+ 19.0 0.4

Radiography: upper lobe 4 (31%) 15 (29.4"/o) 0.9 lower lobe 7 (54%) 27 (52.9%) 0.9 nmlti-lobe 2 (15.4%) 9 (17.6%) 0.8

on admission. The causative organism was identified in 46 cases (72%) as shown in Table II. Mycobacterium tuberculosis was isolated in 13 (20.3 %) of cases. BAL was culture positive in all 13 cases of tuberculosis, but only in seven (54%) sputum samples. The radiographic fea- tures of tuberculous and non-tuberculous cases were similar (Table III).

The second commonest organisms recovered were Streptococcus pneumoniae and Klebsiella pneumoniae sub- species pneumoniae. Two isolates (33.3%) of S. pneu- moniae were penicillin-resistant; all K. pneumoniae were sensitive to aminoglycoside and third generation ce- phalosporins but resistant to amoxycillin and first gen- eration cephalosporins. Viruses were identified in seven patients, four of whom had no other identifiable patho- gens. One case of viral pneumonia progressed to fatal acute respiratory distress syndrome. HIV tests were neg- ative in all the patients.

Table III shows a clinical comparison between tuber- culous and non-tuberculous cases. Serum creatinine was higher in non-tuberculous cases (P<0.014), while serum albumin was lower (P<O.019). The mortality in tuber- culous cases was low (1/13), while 10/51 non-tuber- culous cases died (P-value <0.05). Overall, 52 (83%) of the patients were cured and discharged, while 11 (17%) died. Only four of the 10 subjects who required mech- anical ventilation survived. Antibiotic therapy was pre- scribed in 56% of our patients prior to their admission. Eighty per cent of patients who died received antibiotics before admission. Two of six patients who had S. pneu- moniae died and both had positive blood cultures; two patients with L. pneumophilia also died.

Discussion

About 2 million pilgrims to Mald~ah gather every year in the restricted area of pilgrimage and are mostly housed in tent camps. Overcrowding, exposure to foreign strains of organisms, and physical exhaustion must constitute an obvious case of "extreme circumstances". The pilgrims are mostly elderly and come from countries with a high prevalence of tuberculosis. 4 It is therefore not surprising that findings in this study are different from the usual study of community-acquired pneumonia.

Mycobacterium tuberculosis (20%) was the most com- mon causative organism in our series. In Asian countries, even in the absence of such extreme circumstances, tuberculosis is a relatively common cause of pneumonia. TWo studies in Hong Kong and Singapore this decade found that active tuberculosis accounted for 12% and 20% of community-acquired pneumonia cases, re- spectively.~°' ~1 It has also been shown that the prevalence of tuberculosis and annual risk of infection were three times higher in Saudi Arabian cities which receive pil- grims compared with the national average) 2 This was attributed to contact with pilgrims from poor countries with high prevalence of tuberculous infection.12 Air travel is a well recognized mode for LegionelIa transmission and recently spread of M. tuberculosis has been documented when a passenger with pulmonary tuberculosis was on board.13' 14 Given the findings of this study, this may prove to be a significant mode of infection spread, especially with overcrowded charter flights with many elderly susceptible individuals on board.

The radiological presentation of tuberculosis in our series is of special significance as the lower lobes were exclusively involved in 54% of cases and 30% in the upper lobes and multi-lobar in another 15%; this was not significantly different from non-tuberculous cases (Table III). Another feature was the lack of cavitation. The main explanation, we believe, is the advanced age of these patients. Dahmash et al. ~5 have recently found that in a series of elderly patients with tuberculosis, 61% had lower lobe presentation, and cavitation was seen in only 20%. Moreover, acute tuberculous pneumonia under "extreme circumstances" of overcrowding and poverty tends to be characterized by a "caseous" picture with lobar consolidation and severe systemic effect in a manner that simulates pyogenic pneumonia. 1 Although most of our patients come from areas of increasing (India and South Asia) or high prevalence of HIV infection (Africa), 4 which is known to give rise to atypical presentation of tuberculosis, all of our patients had negative HIV serology.

The other interesting finding was that Gram-negative bacilli accounted for 18.8% of cases, compared with only 9% for S. pneumoniae. Workers in other countries have

306 A. Alzeer e t al.

documented that groups who had previously received antibiotics display a significant decline in the prevalence of S. pneumoniae. 1° Also, patients who are elderly with malnutrition or with unusually severe pneumonia are known to have a greater propensity for Gram-negative pneumonia.16 19 Four patients had Legionella, an organism associated with travel 2° and whose incidence varies with geographical areas. Its presence in our study is important as mortality was high and early antibiotic coverage may reduce fatality. Although M. pneumoniae commonly causes outbreaks in camps, 3'21'22 it accounted for only four cases in our study. Its low incidence may be explained by the fact that our patients were mostly elderly. All our M. pneumoniae cases were under the age of 60 with a mean age of 44 years, compared with a mean age of 64 years for the group. They all made a full recovery.

A 65-year-old patient admitted with respiratory failure requiring mechanical ventilation had Candida albicans cultured from blood, sputum, BAL fluid, and urine. Fur- ther investigation showed prior antibiotic therapy and diabetes mellitus without any other comprising disease, and he failed to respond despite therapy with fluconazole.

In conclusion, severe pneumonia during the pilgrimage to Makkah has features typical of "extreme cir- cumstances" and "camp" pneumonia. The predominant organisms are M. tuberculosis, Gram-negative bacteria, and atypical organisms in that order. Tuberculosis, in particular, develops rapidly and has unusual features including lobar consolidation, a predilection for lower lobes and lack of cavitation. An appropriate initial anti- biotic regimen should include a third generation ce- phalosporin plus erythromycin coupled with a vigorous search for M. tuberculosis in sputum and BAL fuid. A trial of anti-tuberculous drugs might be indicated in cases failing to respond to ordinary antibiotics.

Acknowledgment We would like to acknowledge Dr Hassan A1-Zahrani for his technical support, and Professor Feisal A1-Kassimi and Dr P. Potgietor for re- viewing the manuscript. The secretarial assistance of Mimi S. Gurrea- Villamil is also appreciated.

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