THE WESTERN Journal of Medicine Refer to: Oi1 PA, Chow AW, Roberto RR, et al: An intercity outbreak of meningococcal meningitis in adults. West J Med 128:189-194, Mar 1978
An Intercity Outbreak of Meningococcal Meningitis in Adults PHYLLIS A. OILL, MD, and ANTHONY W. CHOW, MD, Torrance; RONALD R. ROBERTO, MD, Berkeley, and LUCIEN B. GUZE, MD, Los Angeles
An intercity outbreak of meningococcal meningitis occurred in five adults, with the acute onset of symptoms developing in two of the patients after they returned to Los Angeles from the San Francisco Bay area. The secondary attack rate was 36.4 percent in this entirely adult household. The authors review reports of secondary cases in civilian epidemics, as well as recommendations for chemoprophylaxis in household contacts.
AN INTERCITY OUTBREAK of meningococcal meningitis occurred in five adults between April 1 and April 13, 1974 (Table 1). Two patients from the Los Angeles area (Lawndale) admitted to Harbor General Hospital with meningitis said they had visited a friend in the San Francisco Bay area (Mountain View) who also had meningitis. Further investigation showed that an unusual civilian outbreak of meningitis due to a group B strain of Neisseria meningitidis had occurred. The patient in the index case was from Mountain View and four secondary cases resulted from short-term exposure to this patient. In two patients the acute onset of symptoms developed From the Department of Medicine, Harbor General Hospital, Torrance, California; Infectious Disease Section, Department of Health, State of California, Berkeley; Medical and Research Division, Veterans Administration Hospital (Wadsworth), Los Angeles, and University of California, Los Angeles, School of Medicine. Submitted June 17, 1977. Reprint requests to: Phyllis A. Oill, MD, Division of Infectious Disease, Harbor General Hospital, 1000 West Carson Street, Torrance, CA 90509.
after they returned to the Los Angeles area from Mountain View. We report an account of this intercity outbreak, review the reports of secondary cases in civilian epidemics and discuss the recommendations for chemoprophylaxis in household contacts.
Epidemiologic and Laboratory Investigations On April 10 a case of meningococcal meningitis in a patient admitted to Stanford University Hospital was reported to the California Department of Health and it was noted that there was a possibly associated case in a patient in another hospital. The Los Angeles Health Department was notified that contacts of these two patients were in Los Angeles and one had been admitted to Harbor General Hospital. The following series of events was then elucidated (see Table 1). In Mountain View, a community near San Francisco, a household with seven male occupants (three THE WESTERN JOURNAL OF MEDICINE
189
MENINGOCOCCAL MENINGITIS OUTBREAK
slept in bedroom A and four in bedroom B) reported that several members had an influenzalike illness before the outbreak of meningitis. On March 28 four men from Lawndale (including patients 4 and 5) traveled to Mountain View and slept in the household (bedroom B) on March 29 and 30, returning to the Los Angeles area on April 1. Patient 1 (index case), who slept in bedroom A, became acutely ill on March 31. A friend (patient 2), who had visited the household daily, slept at the Mountain View house (bedroom B) that night, actually staying up most of the evening to care for the sick patient (index case). On April 1, the index case patient was admitted to Chope Community Hospital, San Mateo, with meningitis. The men from Lawndale were aware before they returned home that meningitis had been diagnosed in their friend. In patient 2, arthralgias and myalgias developed on April 4, and he was admitted to Stanford University Hospital on April 7 with meningitis. At Harbor General Hospital a patient (patient 4) was admitted with meningitis on the morning of April 8. History from the persons accompanying the latter patient showed that a friend (index case) recently visited by the Harbor General Hospital patient was admitted to hospital in the San Francisco area for meningitis. The physicians at Harbor General Hospital, suspecting meningococcal disease, suggested that any person sleeping in the household of the patient (patient 4) come to the hospital for evaluation. Three persons came to Harbor General Hospital on the evening of April 8 where findings on examination were within normal limits and nasopharyngeal cultures were obtained. On
April 9 one of these persons (patient 5) was admitted to Harbor General Hospital with meningitis. The Santa Clara Health Department had dispatched a public health nurse to the Mountain View household to evaluate the situation, obtain cultures and arrange for chemoprophylaxis. On April 18, patient 3 (slept in bedroom B) was admitted to Santa Clara Valley Medical Center with meningitis. When the Mountain View residence was visited on April 12 by the public health nurse, he had been absent and no one had mentioned him. In Los Angeles a contact tracing team went to the residence of patient 4 and obtained nasopharyngeal cultures from 23 persons who lived in that residence or who had had close contact with the patient. Rifampin, 600 mg per day for four days, was administered after cultures were obtained. All nasopharyngeal cultures taken by this team were negative for Neisseria meningitidis. However, there was a positive nasopharyngeal culture from patient 5 after he was admitted to Harbor General Hospital with meningitis. He was one of the persons who had come to Harbor General Hospital on the evening of April 8. A total of four persons who slept in the Mountain View residence while the index case patient was ill contracted meningococcal meningitis. In none of the 23 household contacts of the secondary case patients from Lawndale (patients 4 and 5) did meningococcal disease develop following exposure in Lawndale. Similarly, meningococcal disease developed in none of the household contacts of patient 2 in Mountain View at a separate
TABLE 1.-Summary of Cases in Mountain View-Lawndale Meningococcal Outbreak Patient Age
Residence
1.. 17
Mountain V;^, PqQffi 1lW + view
2.. 39
Mountain View
3.. 18 4.. 22
Mountain View Lawndale
5
Lawndale
..
19
Date
Date Onset Acute
Date
Admttted
Exposed* Symptoms to Hospital
Index
3/31
4/1
4/4 (daily visits before) Through 4/17 4/18 3/29-3/30 4/7 3/29-3/30 4/9
4/7
4/18 Santa Clara Valley Positive Neisseria meningiMedical Center tidis group B 4/8 Harbor General Positive Negativet Hospital 4/9 Harbor General Positive Neisseria meningiHospital tidis group B
*Dates include nights slept at household when index case patient was present. tPatient received antibiotics before admission.
MARCH 1978 * 128 * 3
tiuis group i
Other
Positive
Cultures
Blood
*:A:.
Stanford University Positive Neisseria meningitidis group B Hospital
CSF- cerebrospinal fluid
190
CSF Culture
CSF Smear
ChopeCommunity Positive NeisseriameningiV \X ^+ ban kiospitai, Mateo
case
^l
3/31
Hospital
Blood
Naso-
pharynx
MENINGOCOCCAL MENINGITIS OUTBREAK
address. All persons involved in this outbreak were monolingual immigrants recently arrived from Mexico. All isolates of Neisseria meningitidis recovered were submitted to the California State Department of Public Health Laboratory for confirmation. All were identified as group B Neisseria meningitidis by biochemical tests and slide agglutination with Neisseria Research Laboratory (NRL) group specific antisera. Minimal inhibitory concentrations to sulfonamide and penicillin were 8.0 Mg per ml and 0.03 .g per ml, respectively. Nasopharyngeal cultures for Neisseria meningitidis among household contacts of patients 4 and 5 in Lawndale were all negative. Contact tracing of household contacts in Mountain View for nasopharyngeal cultures and serological studies were unsuccessful.
Discussion This meningococcal meningitis outbreak is of interest for a number of reasons. It is an outbreak involving two urban areas. Greenfield and Feldman' brought attention to the possible widespread dissemination of meningococcus associated with isolated cases in urban areas and today, with the ease of long distance travel, it is not surprising that persons may be exposed to an infectious process and travel to another area before symptoms develop. Certainly this is not uncommonly encountered with international travelers, and being aware that meningococcal disease can also be involved in this process, physicians should direct attention beyond the immediate family to widening circles of contact. This outbreak occurred among adults exclusively. The report by Young and co-workers2 of meningitis involving adults on one floor of a nursing home is the only other instance, to our knowledge, of a civilian epidemic of meningococcal disease involving adults solely. The peak incidence of meningococcal meningitis during endemic periods occurs in patients between 6 months and 5 years of age, with a second smaller increase due almost entirely to cases of meningococcal disease among military recruits.3'4 During civilian epidemics the very young typically have higher attack rates than older age groups.5'6 There were no children living in the Mountain View and Lawndale households and the adult spread of this disease most probably is related primarily to overcrowding.7-9 Both Kaiser and co-workers9 and Munford and associates'0 showed the importance
of overcrowding in the civilian spread of meningococcal disease. A significant association was found between the total number of occupants in the household and the proportion of contacts infected. In both studies, the rates of infection amoing contacts who slept in the same room as the index patient and those who did not were identical, suggesting that closeness of sleeping contact may be less important a factor in determining the risk of infection to household members than is the total number of members in the same household, and the age of the index case patient. Whether the high attack rate in this all male population is related to the sex of the contacts is speculative. In the Sao Paulo epidemic, attack rates were significantly greater for men than for women aged 20 to 24 years in both preepidemic and epidemic years." Higher rates for young men have been noted in other epidemics.7"12'4 One explanation for the higher rates for young civilian men than for women is the greater contact that young men might have with military friends or situations. We could not ascertain any evidence in our outbreak to support this argument, and neither could the investigators of the Sao Paulo, Brazil, epidemic." The secondary attack rate of 36.3 percent (four of 1 1 contacts) in this outbreak seems unusually high. It has been stated that multiple cases in households are uncommon and, although secondary attack rates in homes are difficult to calculate, rates varying from 0 to 5 percent have been reported.5 However, secondary case rates have been approached differently by various authors. It appears that there are three distinct ways of evaluating secondary cases. The first method is by calculating the number of households with second or third cases in relation to the total number of households with cases of meningitis (Table 2, column A). Viewed in this manner, Norton12 reported the secondary rate in the Detroit epidemic of 1929 to be 3.6 percent, or 34 out of 944 households. Foster and associates,8 in reviewing their experience in Jacksonville, Florida, noted that two of 13 families (15.4 percent) had more than one case of meningitis. Extrapolation of the data from Kaiser and associates9 and Munford and co-workers'0 shows secondary household attack rates of 27.3 percent and 47.3 percent, respectively. Leedom and coworkers'5 reported multiple cases to have ocTHE WESTERN JOURNAL OF MEDICINE
191
MENINGOCOCCAL MENINGITIS OUTBREAK
curred among ten of 290 families at risk (3.4 percent) in Los Angeles County during a 36 month period. Second, secondary attack rates have been calculated by noting the number of second (or third) cases reported from households in which one case had already occurred and relating this to the total number of cases reported during the study period (see Table 2, column B). Norton,12 evaluating his data in this manner, found that of 1,272 cases there were 46 second cases (3.6 percent) from hous-eholds in which one case had already occurred. Among the first 127 cases of meningococcal meningitis in the Indianapolis epidemic of 1929 to 1930, Lee'4 found that there were 29 (22.8 percent) with two or more cases in one family. In the more recent epidemic in Sao Paulo, Munford and associates'0 found the secondary case rate (excluding eight co-primary case pairs) was 18 second cases for 1,152 first cases, or 1.6 percent. These authors mentioned that the frequency of second cases in their study was lower than previously reported from epidemics of meningococcal disease, and that their method of discovering addresses probably underestimated the frequency of secondary cases. Last, secondary attack rates have been calculated by noting the number of second cases in relation to the total number of contacts of the patient in the primary case (Table 2, column C). Contacts are defined as persons living in the same household or persons Who frequently sleep and eat in the same dwelling as the index case patient. A report in 1928 by Hoyne and McEneryl'f alerted physicians to multiple cases of meningococcal
disease within households. Two secondary cases occurred in a family of eight following identification of the index case for a calculated attack rate of 28.6 percent (two of seven contacts). Norton12 noted that there were 46 secondary cases among 6,416 contacts (0.7 percent). In an extensive evaluation of 9,668 contacts of 5,885 primary case patients in the Chile epidemic (1941 to 1942), Pizzi7 found an overall attack rate of 2.6 percent (247 secondary cases). Calculation of the data presented by Foster and co-workers8 of multiple cases in two households shows a secondary rate of 40 percent (two of five contacts) and 20 percent (two of ten contacts), respectively. Kaiser and co-workers9 from Florida found that five of 85 close contacts (5.9 percent) contracted meningococcal disease. In their study, if one looks at household contacts only (excluding a day-care nursery), then four secondary cases occurred out of 71 contacts for a rate of 5.6 percent. It is in this latter manner that we have calculated an attack rate of 36.4 percent, with four secondary cases of meningococcal disease occurring in 11 contacts of the index case. It is difficult to compare the risk to particular household contacts of patients with meningococcal meningitis by using diverse means of generating secondary attack rates. It is the third method of evaluation cited above' that probably most closely approaches the attack rate for close contacts. However, the studies are too small and attack rates are too varied (0.7 percent to 40 percent) to yield useful information regarding the risk of contacting meningococcal disease for family members in a particular household. Lee-
TABLE 2.-Summary of Secondary Cases in Civillan Meningococcal Outbreaks
Author
A Number of Households With Second Cases/Total Number of Households
B Numberof Secondary Cases in Household With Primary Case/Tot4l Number of
Primary Cases
Hoyne and McEnery". ......... Norton .................... Lee . ...................... Pizzi7 ....................... Foster, et aP .................
NA 34/944* (3.6%) NA NA 2/13 (15.4%)
NA 46/1,272 (3.6%) 29/127 (22.8%)
Leedom, et al. ............... Kaiser, et al ................. Munford, et al"' .............. Oill, et al ...................
10/290 (3.4%) 3/11* (27.3%)
NA NA 18/1,152 (1.6%) NA
26/55* (47.3%)
NA-not available
*Calculated from published data
192
MARCH 1978 * 128 * 3
NA
NA NA
C
Number of Secondary Cases/Number of Contacts of Primary Case
2/7 (28.6%) 46/6,416 (0.7%) NA 247/9,668 (2.6%) Family 1-2/5* (40%) Family 2-2/10* (20%) NA 4/71* (5.6%) NA 4/11 (36.4%)
MENINGOCOCCAL MENINGITIS OUTBREAK
dom and associates,15 concerned with this issue, calculated the average number of persons residing in the same household of each patient with meningitis, based on an unselected sample of 152 of 290 (52.4 percent) families. When this figure was used to estimate the population at risk, the risk of multiple cases among household contacts of patients with meningococcal disease was about 992 per 100,000 as contrasted with the average incidence in Los Angeles County during the reported period of time (1963 through 1965) of 2.09 per 100,000. These authors make the point that this incidence would indicate a 457-fold increase in risk for household members. Nevertheless, more specific data must be generated regarding the risk to household members before the actual secondary family attack rate can be known. The question of household risk has implications for a clinician faced with a family in which there is a case of meningococcal meningitis. Since 23 percent of case isolates from the United States recently studied at the Center for Disease Control were sulfa-resistant, and all were sensitive to rifampin, administration of rifampin is recommended as prophylaxis for family contacts of persons with meningococcal meningitis, unless the infecting strain is known to be sensitive to 10 jug per ml of sulfadiazine.17 However, rifampin-resistant mutants have emerged,18-20 and a secondary case of meningococcal meningitis in a family following rifampin prophylaxis has been reported.21 Minocycline, although effective in reducing the carrier rate,19 has considerable side effects associated with its use.22'23 Combination therapy with nfampin and minocycline had its first trial in naval recruits with good results and few side effects.24 However, in a study of Brazilian families, Munford and associates25 found that although there was eradication of the organism in all carriers treated, there were significant side effects in 33 percent of the subjects. So it appears that a fully efficacious chemoprophylactic agent is not yet available; because of this, Artenstein26 has suggested that if the organism is sulfonamideresistant, or if no data are available, antibiotic prophylaxis is not recommended. However, a recent report from the Meningococcal Surveillance Group27 stated that the need for prophylactic drugs for household contacts was supported by their data which showed an attack rate among household contacts to be 500 to 800 times greater than that determined for the general population. Additionally, their data suggest that an appropri-
ately chosen prophylactic agent is probably effective in reducing this risk, and they recommend antibiotic prophylaxis for household contacts. Polysaccharide vaccines effective against meningococcal serogroups A and C are now licensed in the United States and are available in monovalent and bivalent forms.27 After administration, about a week is required for adequate antibody response to develop. Since about half the secondary cases of meningococcal disease in household contacts occur more than five days after the primary case, vaccination may be effective if the etiologic meningococcus is of group A or C. Vaccination is, therefore, recommended by some as an adjunct to chemoprophylaxis.27 It should be noted, however, that the effectiveness of this approach has not been established, and that vaccine prophylaxis may provide little or no added protection over prompt rifampin prophylaxis. Additionally, serogroup B strains cause most civilian cases27 and no satisfactory group B polysaccharide vaccine is yet available. In our study, all available contacts to the index case patient in Mountain View and contacts of the secondary case patient in Lawndale were treated with rifampin. None of the contact cultures were positive for Neisseria meningitidis except for the patient (patient 5) admitted to hospital with meningitis. Until more definitive secondary attack rates can be ascertained, it appears that household contacts are at higher risk and should receive chemoprophylaxis with rifampin. Although primary attention has been directed towards the younger adult contacts in the past, our experience suggests that adult contacts under crowded situations may be similarly at risk. Finally, since no drug is completely effective for chemoprophylaxis, close medical observation remains an important factor in management of household and intimate contacts to meningococcal disease. REFERENCES 1. Greenfield S, Feldman HA: Familial carriers and meningococcal meningitis. N Engl J Med 277:497-502, Sep 1967 2. Young LS, LaForce FM, Head JJ, et al: A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med 287:5-9, Jul 1972 3. Kaufman B, Levy H, Zaleznak BD, et al: Statistical analysis of 242 cases of meningococcus meningitis. J Pediatr 38:705-716, Jun 1951 4. Goldschneider I, Gotschlich EC, Artenstein MS: Human immunity to the meningococcus-I. The role of humoral antibodies. J Exper Med 129:1307-1326, Jun 1969 5. Feldman HA: Some recollections of the meningococcal diseases-The first Harry F. Dowling lecture. JAMA 220:1107-1112, May 1972 6. Beeson PB, Westerman E: Cerebrospinal fever: Analysis of 3,575 case reports, with special reference to sulphonamide therapy. Br Med J 1:497-500, Apr 1943 7. Pizzi M: A severe epidemic of meningococcus meningitis in Chile, 1941-1942. Am J Public Health 34:231-238, Mar 1944
THE WESTERN JOURNAL OF MEDICINE
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MENINGOCOCCAL MENINGITIS OUTBREAK 8. Foster MT Jr, Sanders E, Ginter M: Epidemiology of sulfonamide-resistant meningococcal infections in a civilian population. Am J Epidemiol 93:346-353, May 1971 9. Kaiser AB, Hennekens CH, Saslaw MS, et al: Seroepidemiology and chemoprophylaxis of disease due to sulfonamide-resistant Neisseria meningitidis in a civilian population. J Infect Dis 130: 217-224, Sep 1974 10. Munford RS, Taunay A de E, Souza De Morais J, et al: Spread of meningococcal infection within households. Lancet 1:1275-1278, Jun 1974 11. Souza De Morais J, Munford RS, Risi JB, et al: Epidemic disease due to serogroup C Neisseria meningitidis in Sa6 Paulo, Brazil. J Infect Dis 129:568-571, May 1974 12. Norton JF: Meningococcus meningitis in Detroit: 19281929-V. Secondary cases. J Prev Med 5:365-367, Sep 1931 13. Levy GJ: Meningococcus meningitis: A study of the Memphis outbreak in 1930. South Med J 24:232-238, Mar 1931 14. Lee WW: Epidemic meningitis in Indianapolis, 1929-1930. J Prey Med 5:203-209, May 1931 15. Leedom JM, Ivlev D, Mathies AW, Jr, et al: The problem of sulfadiazine-resistant meningococci. Antimicrob Agents Chemo 6:281-292, 1966 16. Hoyne A, McEnery ET: Multiple cases of epidemic meningitis in the same family. Arch Pediatr 46:699-702, Nov 1929 17. Center for Disease Control, Morbidity and Mortality Weekly Report 24:455, 1976
18. Weidmer CE, Dunkel TB, Pettyjohn FS, et al: Effectiveness of rifampin in eradicating meningococcal carrier state in a relatively closed population: Emergence of resistant strains. J Infect Dis 124:172-178, Aug 1971 19. Guttler RB, Counts GW, Avent CK, et al: Effort of rifampin and minocycline on meningococcal carrier rates. J Infect Dis 124:199-205, Aug 1971 20. Eickhoff TC: In-vitro and in-vivo studies of resistance to rifampin in meningococci. J Infect Dis 123:414-420, Apr 1971 21. Khuri-Bulos N: Meningococcal meningitis following rifampin prophylaxis. Am J Dis Child 126:689-691, Nov 1973 22. Williams DN, Laughlin LW, Lee Y-H: Minocycline: Possible vestibular side-effects. Lancet 2:744-746, Sep 1974 23. Center for Disease Control, Morbidity and Mortality Weekly Report 25:31, 1976 24. Devine LF, Pollard RB, Krumpe PE, et al: Field trial of the efficacy of a previously proposed regimen using minocycline and rifampin sequentially for the elimination of meningococci fromn healthy carriers. Am J Epidemiol 97:394 401, Jun 1973 25. Munford RS, Sussuarana De Vasconcelos ZJ, Phyllips CJ, et al: Eradication of carriage of Neisseria meningitidis in families: A study in Brazil. J Infect Dis 129:644-649, Jun 1974 26. Artenstein MS: Prophylaxis for meningococcal disease. JAMA 231:1035-1037, Mar 1975 27. Center for Disease Control, Morbidity and Mortality Weekly Report 24:381-382, Nov 1975
Esophageal Pain Misdiagnosed as Angina Pectoris A PATIENT may say that he or she has pain in the chest and this pain may be described as similar to the pain of angina pectoris. . . . Physicians may do a great disservice to their patients if they do not clearly define the nature of chest pain. Angina pectoris is, of course, typically caused by myocardial ischemia and is a deep, frightening, sometimes crushing type of pain in the chest which may radiate to the jaw, to the shoulders or down the arm. Esophageal pain is extremely similar in its descriptions and ... in its radiation. The only way we can really distinguish the one from the other is by noting the associations. The situation arising from the esophagus and causing symptoms is usually associated, at some point or other in the history, with dysphagia. The pain of heart disease is usually, but not always, associated with activity; it may be associated with eating.... With these associations we can distinguish one from the other and it is extremely important to do so. It would be a great disservice if a patient has myocardial ischemia and we treat it lightly. . . We do a patient just as great a disservice if esophageal spasm is the problem and we treat it too seriously by calling it angina pectoris. There may be as many lives being ruined in the social and personal sense by having a condition misdiagnosed as angina pectoris as there are lives threatened by a failure to diagnose angina pectoris. .
-ALASTAIR M. CONNELL, MD, Cincinnati Extracted from Audio-Digest Internal Medicine, Vol. 24, No. 9, in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 East Chevy Chase Drive, Glendale, CA 91206.
194
MARCH 1978 * 128 * 3
An Intercity Outbreak of Meningococcal Meningitis in Adults PHYLLIS A. OILL, MD, and ANTHONY W. CHOW, MD, Torrance; RONALD R. ROBERTO, MD, Berkeley, and LUCIEN B. GUZE, MD, Los Angeles
An intercity outbreak of meningococcal meningitis occurred in five adults, with the acute onset of symptoms developing in two of the patients after they returned to Los Angeles from the San Francisco Bay area. The secondary attack rate was 36.4 percent in this entirely adult household. The authors review reports of secondary cases in civilian epidemics, as well as recommendations for chemoprophylaxis in household contacts.
AN INTERCITY OUTBREAK of meningococcal meningitis occurred in five adults between April 1 and April 13, 1974 (Table 1). Two patients from the Los Angeles area (Lawndale) admitted to Harbor General Hospital with meningitis said they had visited a friend in the San Francisco Bay area (Mountain View) who also had meningitis. Further investigation showed that an unusual civilian outbreak of meningitis due to a group B strain of Neisseria meningitidis had occurred. The patient in the index case was from Mountain View and four secondary cases resulted from short-term exposure to this patient. In two patients the acute onset of symptoms developed From the Department of Medicine, Harbor General Hospital, Torrance, California; Infectious Disease Section, Department of Health, State of California, Berkeley; Medical and Research Division, Veterans Administration Hospital (Wadsworth), Los Angeles, and University of California, Los Angeles, School of Medicine. Submitted June 17, 1977. Reprint requests to: Phyllis A. Oill, MD, Division of Infectious Disease, Harbor General Hospital, 1000 West Carson Street, Torrance, CA 90509.
after they returned to the Los Angeles area from Mountain View. We report an account of this intercity outbreak, review the reports of secondary cases in civilian epidemics and discuss the recommendations for chemoprophylaxis in household contacts.
Epidemiologic and Laboratory Investigations On April 10 a case of meningococcal meningitis in a patient admitted to Stanford University Hospital was reported to the California Department of Health and it was noted that there was a possibly associated case in a patient in another hospital. The Los Angeles Health Department was notified that contacts of these two patients were in Los Angeles and one had been admitted to Harbor General Hospital. The following series of events was then elucidated (see Table 1). In Mountain View, a community near San Francisco, a household with seven male occupants (three THE WESTERN JOURNAL OF MEDICINE
189
MENINGOCOCCAL MENINGITIS OUTBREAK
slept in bedroom A and four in bedroom B) reported that several members had an influenzalike illness before the outbreak of meningitis. On March 28 four men from Lawndale (including patients 4 and 5) traveled to Mountain View and slept in the household (bedroom B) on March 29 and 30, returning to the Los Angeles area on April 1. Patient 1 (index case), who slept in bedroom A, became acutely ill on March 31. A friend (patient 2), who had visited the household daily, slept at the Mountain View house (bedroom B) that night, actually staying up most of the evening to care for the sick patient (index case). On April 1, the index case patient was admitted to Chope Community Hospital, San Mateo, with meningitis. The men from Lawndale were aware before they returned home that meningitis had been diagnosed in their friend. In patient 2, arthralgias and myalgias developed on April 4, and he was admitted to Stanford University Hospital on April 7 with meningitis. At Harbor General Hospital a patient (patient 4) was admitted with meningitis on the morning of April 8. History from the persons accompanying the latter patient showed that a friend (index case) recently visited by the Harbor General Hospital patient was admitted to hospital in the San Francisco area for meningitis. The physicians at Harbor General Hospital, suspecting meningococcal disease, suggested that any person sleeping in the household of the patient (patient 4) come to the hospital for evaluation. Three persons came to Harbor General Hospital on the evening of April 8 where findings on examination were within normal limits and nasopharyngeal cultures were obtained. On
April 9 one of these persons (patient 5) was admitted to Harbor General Hospital with meningitis. The Santa Clara Health Department had dispatched a public health nurse to the Mountain View household to evaluate the situation, obtain cultures and arrange for chemoprophylaxis. On April 18, patient 3 (slept in bedroom B) was admitted to Santa Clara Valley Medical Center with meningitis. When the Mountain View residence was visited on April 12 by the public health nurse, he had been absent and no one had mentioned him. In Los Angeles a contact tracing team went to the residence of patient 4 and obtained nasopharyngeal cultures from 23 persons who lived in that residence or who had had close contact with the patient. Rifampin, 600 mg per day for four days, was administered after cultures were obtained. All nasopharyngeal cultures taken by this team were negative for Neisseria meningitidis. However, there was a positive nasopharyngeal culture from patient 5 after he was admitted to Harbor General Hospital with meningitis. He was one of the persons who had come to Harbor General Hospital on the evening of April 8. A total of four persons who slept in the Mountain View residence while the index case patient was ill contracted meningococcal meningitis. In none of the 23 household contacts of the secondary case patients from Lawndale (patients 4 and 5) did meningococcal disease develop following exposure in Lawndale. Similarly, meningococcal disease developed in none of the household contacts of patient 2 in Mountain View at a separate
TABLE 1.-Summary of Cases in Mountain View-Lawndale Meningococcal Outbreak Patient Age
Residence
1.. 17
Mountain V;^, PqQffi 1lW + view
2.. 39
Mountain View
3.. 18 4.. 22
Mountain View Lawndale
5
Lawndale
..
19
Date
Date Onset Acute
Date
Admttted
Exposed* Symptoms to Hospital
Index
3/31
4/1
4/4 (daily visits before) Through 4/17 4/18 3/29-3/30 4/7 3/29-3/30 4/9
4/7
4/18 Santa Clara Valley Positive Neisseria meningiMedical Center tidis group B 4/8 Harbor General Positive Negativet Hospital 4/9 Harbor General Positive Neisseria meningiHospital tidis group B
*Dates include nights slept at household when index case patient was present. tPatient received antibiotics before admission.
MARCH 1978 * 128 * 3
tiuis group i
Other
Positive
Cultures
Blood
*:A:.
Stanford University Positive Neisseria meningitidis group B Hospital
CSF- cerebrospinal fluid
190
CSF Culture
CSF Smear
ChopeCommunity Positive NeisseriameningiV \X ^+ ban kiospitai, Mateo
case
^l
3/31
Hospital
Blood
Naso-
pharynx
MENINGOCOCCAL MENINGITIS OUTBREAK
address. All persons involved in this outbreak were monolingual immigrants recently arrived from Mexico. All isolates of Neisseria meningitidis recovered were submitted to the California State Department of Public Health Laboratory for confirmation. All were identified as group B Neisseria meningitidis by biochemical tests and slide agglutination with Neisseria Research Laboratory (NRL) group specific antisera. Minimal inhibitory concentrations to sulfonamide and penicillin were 8.0 Mg per ml and 0.03 .g per ml, respectively. Nasopharyngeal cultures for Neisseria meningitidis among household contacts of patients 4 and 5 in Lawndale were all negative. Contact tracing of household contacts in Mountain View for nasopharyngeal cultures and serological studies were unsuccessful.
Discussion This meningococcal meningitis outbreak is of interest for a number of reasons. It is an outbreak involving two urban areas. Greenfield and Feldman' brought attention to the possible widespread dissemination of meningococcus associated with isolated cases in urban areas and today, with the ease of long distance travel, it is not surprising that persons may be exposed to an infectious process and travel to another area before symptoms develop. Certainly this is not uncommonly encountered with international travelers, and being aware that meningococcal disease can also be involved in this process, physicians should direct attention beyond the immediate family to widening circles of contact. This outbreak occurred among adults exclusively. The report by Young and co-workers2 of meningitis involving adults on one floor of a nursing home is the only other instance, to our knowledge, of a civilian epidemic of meningococcal disease involving adults solely. The peak incidence of meningococcal meningitis during endemic periods occurs in patients between 6 months and 5 years of age, with a second smaller increase due almost entirely to cases of meningococcal disease among military recruits.3'4 During civilian epidemics the very young typically have higher attack rates than older age groups.5'6 There were no children living in the Mountain View and Lawndale households and the adult spread of this disease most probably is related primarily to overcrowding.7-9 Both Kaiser and co-workers9 and Munford and associates'0 showed the importance
of overcrowding in the civilian spread of meningococcal disease. A significant association was found between the total number of occupants in the household and the proportion of contacts infected. In both studies, the rates of infection amoing contacts who slept in the same room as the index patient and those who did not were identical, suggesting that closeness of sleeping contact may be less important a factor in determining the risk of infection to household members than is the total number of members in the same household, and the age of the index case patient. Whether the high attack rate in this all male population is related to the sex of the contacts is speculative. In the Sao Paulo epidemic, attack rates were significantly greater for men than for women aged 20 to 24 years in both preepidemic and epidemic years." Higher rates for young men have been noted in other epidemics.7"12'4 One explanation for the higher rates for young civilian men than for women is the greater contact that young men might have with military friends or situations. We could not ascertain any evidence in our outbreak to support this argument, and neither could the investigators of the Sao Paulo, Brazil, epidemic." The secondary attack rate of 36.3 percent (four of 1 1 contacts) in this outbreak seems unusually high. It has been stated that multiple cases in households are uncommon and, although secondary attack rates in homes are difficult to calculate, rates varying from 0 to 5 percent have been reported.5 However, secondary case rates have been approached differently by various authors. It appears that there are three distinct ways of evaluating secondary cases. The first method is by calculating the number of households with second or third cases in relation to the total number of households with cases of meningitis (Table 2, column A). Viewed in this manner, Norton12 reported the secondary rate in the Detroit epidemic of 1929 to be 3.6 percent, or 34 out of 944 households. Foster and associates,8 in reviewing their experience in Jacksonville, Florida, noted that two of 13 families (15.4 percent) had more than one case of meningitis. Extrapolation of the data from Kaiser and associates9 and Munford and co-workers'0 shows secondary household attack rates of 27.3 percent and 47.3 percent, respectively. Leedom and coworkers'5 reported multiple cases to have ocTHE WESTERN JOURNAL OF MEDICINE
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curred among ten of 290 families at risk (3.4 percent) in Los Angeles County during a 36 month period. Second, secondary attack rates have been calculated by noting the number of second (or third) cases reported from households in which one case had already occurred and relating this to the total number of cases reported during the study period (see Table 2, column B). Norton,12 evaluating his data in this manner, found that of 1,272 cases there were 46 second cases (3.6 percent) from hous-eholds in which one case had already occurred. Among the first 127 cases of meningococcal meningitis in the Indianapolis epidemic of 1929 to 1930, Lee'4 found that there were 29 (22.8 percent) with two or more cases in one family. In the more recent epidemic in Sao Paulo, Munford and associates'0 found the secondary case rate (excluding eight co-primary case pairs) was 18 second cases for 1,152 first cases, or 1.6 percent. These authors mentioned that the frequency of second cases in their study was lower than previously reported from epidemics of meningococcal disease, and that their method of discovering addresses probably underestimated the frequency of secondary cases. Last, secondary attack rates have been calculated by noting the number of second cases in relation to the total number of contacts of the patient in the primary case (Table 2, column C). Contacts are defined as persons living in the same household or persons Who frequently sleep and eat in the same dwelling as the index case patient. A report in 1928 by Hoyne and McEneryl'f alerted physicians to multiple cases of meningococcal
disease within households. Two secondary cases occurred in a family of eight following identification of the index case for a calculated attack rate of 28.6 percent (two of seven contacts). Norton12 noted that there were 46 secondary cases among 6,416 contacts (0.7 percent). In an extensive evaluation of 9,668 contacts of 5,885 primary case patients in the Chile epidemic (1941 to 1942), Pizzi7 found an overall attack rate of 2.6 percent (247 secondary cases). Calculation of the data presented by Foster and co-workers8 of multiple cases in two households shows a secondary rate of 40 percent (two of five contacts) and 20 percent (two of ten contacts), respectively. Kaiser and co-workers9 from Florida found that five of 85 close contacts (5.9 percent) contracted meningococcal disease. In their study, if one looks at household contacts only (excluding a day-care nursery), then four secondary cases occurred out of 71 contacts for a rate of 5.6 percent. It is in this latter manner that we have calculated an attack rate of 36.4 percent, with four secondary cases of meningococcal disease occurring in 11 contacts of the index case. It is difficult to compare the risk to particular household contacts of patients with meningococcal meningitis by using diverse means of generating secondary attack rates. It is the third method of evaluation cited above' that probably most closely approaches the attack rate for close contacts. However, the studies are too small and attack rates are too varied (0.7 percent to 40 percent) to yield useful information regarding the risk of contacting meningococcal disease for family members in a particular household. Lee-
TABLE 2.-Summary of Secondary Cases in Civillan Meningococcal Outbreaks
Author
A Number of Households With Second Cases/Total Number of Households
B Numberof Secondary Cases in Household With Primary Case/Tot4l Number of
Primary Cases
Hoyne and McEnery". ......... Norton .................... Lee . ...................... Pizzi7 ....................... Foster, et aP .................
NA 34/944* (3.6%) NA NA 2/13 (15.4%)
NA 46/1,272 (3.6%) 29/127 (22.8%)
Leedom, et al. ............... Kaiser, et al ................. Munford, et al"' .............. Oill, et al ...................
10/290 (3.4%) 3/11* (27.3%)
NA NA 18/1,152 (1.6%) NA
26/55* (47.3%)
NA-not available
*Calculated from published data
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NA
NA NA
C
Number of Secondary Cases/Number of Contacts of Primary Case
2/7 (28.6%) 46/6,416 (0.7%) NA 247/9,668 (2.6%) Family 1-2/5* (40%) Family 2-2/10* (20%) NA 4/71* (5.6%) NA 4/11 (36.4%)
MENINGOCOCCAL MENINGITIS OUTBREAK
dom and associates,15 concerned with this issue, calculated the average number of persons residing in the same household of each patient with meningitis, based on an unselected sample of 152 of 290 (52.4 percent) families. When this figure was used to estimate the population at risk, the risk of multiple cases among household contacts of patients with meningococcal disease was about 992 per 100,000 as contrasted with the average incidence in Los Angeles County during the reported period of time (1963 through 1965) of 2.09 per 100,000. These authors make the point that this incidence would indicate a 457-fold increase in risk for household members. Nevertheless, more specific data must be generated regarding the risk to household members before the actual secondary family attack rate can be known. The question of household risk has implications for a clinician faced with a family in which there is a case of meningococcal meningitis. Since 23 percent of case isolates from the United States recently studied at the Center for Disease Control were sulfa-resistant, and all were sensitive to rifampin, administration of rifampin is recommended as prophylaxis for family contacts of persons with meningococcal meningitis, unless the infecting strain is known to be sensitive to 10 jug per ml of sulfadiazine.17 However, rifampin-resistant mutants have emerged,18-20 and a secondary case of meningococcal meningitis in a family following rifampin prophylaxis has been reported.21 Minocycline, although effective in reducing the carrier rate,19 has considerable side effects associated with its use.22'23 Combination therapy with nfampin and minocycline had its first trial in naval recruits with good results and few side effects.24 However, in a study of Brazilian families, Munford and associates25 found that although there was eradication of the organism in all carriers treated, there were significant side effects in 33 percent of the subjects. So it appears that a fully efficacious chemoprophylactic agent is not yet available; because of this, Artenstein26 has suggested that if the organism is sulfonamideresistant, or if no data are available, antibiotic prophylaxis is not recommended. However, a recent report from the Meningococcal Surveillance Group27 stated that the need for prophylactic drugs for household contacts was supported by their data which showed an attack rate among household contacts to be 500 to 800 times greater than that determined for the general population. Additionally, their data suggest that an appropri-
ately chosen prophylactic agent is probably effective in reducing this risk, and they recommend antibiotic prophylaxis for household contacts. Polysaccharide vaccines effective against meningococcal serogroups A and C are now licensed in the United States and are available in monovalent and bivalent forms.27 After administration, about a week is required for adequate antibody response to develop. Since about half the secondary cases of meningococcal disease in household contacts occur more than five days after the primary case, vaccination may be effective if the etiologic meningococcus is of group A or C. Vaccination is, therefore, recommended by some as an adjunct to chemoprophylaxis.27 It should be noted, however, that the effectiveness of this approach has not been established, and that vaccine prophylaxis may provide little or no added protection over prompt rifampin prophylaxis. Additionally, serogroup B strains cause most civilian cases27 and no satisfactory group B polysaccharide vaccine is yet available. In our study, all available contacts to the index case patient in Mountain View and contacts of the secondary case patient in Lawndale were treated with rifampin. None of the contact cultures were positive for Neisseria meningitidis except for the patient (patient 5) admitted to hospital with meningitis. Until more definitive secondary attack rates can be ascertained, it appears that household contacts are at higher risk and should receive chemoprophylaxis with rifampin. Although primary attention has been directed towards the younger adult contacts in the past, our experience suggests that adult contacts under crowded situations may be similarly at risk. Finally, since no drug is completely effective for chemoprophylaxis, close medical observation remains an important factor in management of household and intimate contacts to meningococcal disease. REFERENCES 1. Greenfield S, Feldman HA: Familial carriers and meningococcal meningitis. N Engl J Med 277:497-502, Sep 1967 2. Young LS, LaForce FM, Head JJ, et al: A simultaneous outbreak of meningococcal and influenza infections. N Engl J Med 287:5-9, Jul 1972 3. Kaufman B, Levy H, Zaleznak BD, et al: Statistical analysis of 242 cases of meningococcus meningitis. J Pediatr 38:705-716, Jun 1951 4. Goldschneider I, Gotschlich EC, Artenstein MS: Human immunity to the meningococcus-I. The role of humoral antibodies. J Exper Med 129:1307-1326, Jun 1969 5. Feldman HA: Some recollections of the meningococcal diseases-The first Harry F. Dowling lecture. JAMA 220:1107-1112, May 1972 6. Beeson PB, Westerman E: Cerebrospinal fever: Analysis of 3,575 case reports, with special reference to sulphonamide therapy. Br Med J 1:497-500, Apr 1943 7. Pizzi M: A severe epidemic of meningococcus meningitis in Chile, 1941-1942. Am J Public Health 34:231-238, Mar 1944
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MENINGOCOCCAL MENINGITIS OUTBREAK 8. Foster MT Jr, Sanders E, Ginter M: Epidemiology of sulfonamide-resistant meningococcal infections in a civilian population. Am J Epidemiol 93:346-353, May 1971 9. Kaiser AB, Hennekens CH, Saslaw MS, et al: Seroepidemiology and chemoprophylaxis of disease due to sulfonamide-resistant Neisseria meningitidis in a civilian population. J Infect Dis 130: 217-224, Sep 1974 10. Munford RS, Taunay A de E, Souza De Morais J, et al: Spread of meningococcal infection within households. Lancet 1:1275-1278, Jun 1974 11. Souza De Morais J, Munford RS, Risi JB, et al: Epidemic disease due to serogroup C Neisseria meningitidis in Sa6 Paulo, Brazil. J Infect Dis 129:568-571, May 1974 12. Norton JF: Meningococcus meningitis in Detroit: 19281929-V. Secondary cases. J Prev Med 5:365-367, Sep 1931 13. Levy GJ: Meningococcus meningitis: A study of the Memphis outbreak in 1930. South Med J 24:232-238, Mar 1931 14. Lee WW: Epidemic meningitis in Indianapolis, 1929-1930. J Prey Med 5:203-209, May 1931 15. Leedom JM, Ivlev D, Mathies AW, Jr, et al: The problem of sulfadiazine-resistant meningococci. Antimicrob Agents Chemo 6:281-292, 1966 16. Hoyne A, McEnery ET: Multiple cases of epidemic meningitis in the same family. Arch Pediatr 46:699-702, Nov 1929 17. Center for Disease Control, Morbidity and Mortality Weekly Report 24:455, 1976
18. Weidmer CE, Dunkel TB, Pettyjohn FS, et al: Effectiveness of rifampin in eradicating meningococcal carrier state in a relatively closed population: Emergence of resistant strains. J Infect Dis 124:172-178, Aug 1971 19. Guttler RB, Counts GW, Avent CK, et al: Effort of rifampin and minocycline on meningococcal carrier rates. J Infect Dis 124:199-205, Aug 1971 20. Eickhoff TC: In-vitro and in-vivo studies of resistance to rifampin in meningococci. J Infect Dis 123:414-420, Apr 1971 21. Khuri-Bulos N: Meningococcal meningitis following rifampin prophylaxis. Am J Dis Child 126:689-691, Nov 1973 22. Williams DN, Laughlin LW, Lee Y-H: Minocycline: Possible vestibular side-effects. Lancet 2:744-746, Sep 1974 23. Center for Disease Control, Morbidity and Mortality Weekly Report 25:31, 1976 24. Devine LF, Pollard RB, Krumpe PE, et al: Field trial of the efficacy of a previously proposed regimen using minocycline and rifampin sequentially for the elimination of meningococci fromn healthy carriers. Am J Epidemiol 97:394 401, Jun 1973 25. Munford RS, Sussuarana De Vasconcelos ZJ, Phyllips CJ, et al: Eradication of carriage of Neisseria meningitidis in families: A study in Brazil. J Infect Dis 129:644-649, Jun 1974 26. Artenstein MS: Prophylaxis for meningococcal disease. JAMA 231:1035-1037, Mar 1975 27. Center for Disease Control, Morbidity and Mortality Weekly Report 24:381-382, Nov 1975
Esophageal Pain Misdiagnosed as Angina Pectoris A PATIENT may say that he or she has pain in the chest and this pain may be described as similar to the pain of angina pectoris. . . . Physicians may do a great disservice to their patients if they do not clearly define the nature of chest pain. Angina pectoris is, of course, typically caused by myocardial ischemia and is a deep, frightening, sometimes crushing type of pain in the chest which may radiate to the jaw, to the shoulders or down the arm. Esophageal pain is extremely similar in its descriptions and ... in its radiation. The only way we can really distinguish the one from the other is by noting the associations. The situation arising from the esophagus and causing symptoms is usually associated, at some point or other in the history, with dysphagia. The pain of heart disease is usually, but not always, associated with activity; it may be associated with eating.... With these associations we can distinguish one from the other and it is extremely important to do so. It would be a great disservice if a patient has myocardial ischemia and we treat it lightly. . . We do a patient just as great a disservice if esophageal spasm is the problem and we treat it too seriously by calling it angina pectoris. There may be as many lives being ruined in the social and personal sense by having a condition misdiagnosed as angina pectoris as there are lives threatened by a failure to diagnose angina pectoris. .
-ALASTAIR M. CONNELL, MD, Cincinnati Extracted from Audio-Digest Internal Medicine, Vol. 24, No. 9, in the Audio-Digest Foundation's subscription series of taperecorded programs. For subscription information: 1577 East Chevy Chase Drive, Glendale, CA 91206.
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