CATEGORY TITLE
Cross
Reactivity Observed in Patients Whose Blood Samples Tested Positive for Leptospira
IgM and Dengue IgM Antibodies
Sushil
Shah, Nilesh Shah
In modern
times, when a patient presents with very high fever and toxicity, both the
public and the medical practitioners become very alert to the diagnosis of
either dengue or leptospirosis. And why not? Both are ‘killer’
diseases.
Metropolis Laboratory is one of the leading referral laboratories of the country
having a chain of laboratories at Mumbai, Chennai, Jaipur, Cochin, Trichur
and Dubai. The chain analyses over 10,000 tests per day. The laboratory is
of an international standard and compares with the best in the world.
One of the aims of Metropolis Laboratory, which has a large number of medical
staff, is to bring out any information which will help the clinicians.
We collected statistics of the blood samples sent to our laboratory during
last one year.
Material and Results
Tables 1 and 6 show the results of these tests carried out in 4495 blood samples
over the last one year in Mumbai (including suburbs).
TABLE
1
Levels of positivity
|
 |
| |
Total
|
Negative
|
%
|
Weakly
Positive |
%
|
Moderate |
% |
Strongly
positive |
% |
 |
Leptospira
- IgM
|
1743 |
1227 |
71 |
243 |
14 |
182 |
10 |
91 |
5.3 |
|
| Dengue
- IgM |
2752 |
1417 |
51.4 |
364 |
13.2 |
365 |
13 |
606 |
22 |
|
| |
|
|
|
|
|
|
|
|
|
|
TABLE
2
Statistical report + Dengue + Leptospira |
|
| |
Total
Samples |
Positive |
|
Dengue-IgM+
Leptospira - IgM |
733
Total patients tested for both |
104
Positive for
both |
|
TABLE
5
Zonewise incidence - positive |
|
| Test |
Total
+ve Sample |
Zone
code |
Zone
Name |
Zone
Desc |
Samples |
|
| Leptospira
- IgM |
481 |
007 |
Direct |
Direct |
0 |
|
| |
|
1 |
Marine
lines to Colaba (Ajay)
|
South
Bombay |
12 |
| |
|
2 |
Thane
West
|
Central
|
5 |
| |
|
3 |
New
Bombay Nerul Govandi
|
Central
|
34 |
| |
|
4 |
Ulhasnagar
Ambernath Bada
|
Central
|
0 |
| |
|
5 |
Kalyan
|
Cental
|
4 |
| |
|
6 |
Thane
— East
|
Central
|
16 |
| |
|
7 |
Mulund
|
Central
|
16 |
| |
|
8 |
Bhandup,
Vikroli, Kanjurmarg
|
Cental
|
12 |
| |
|
9 |
Ghatkopar
|
Central
|
27 |
| |
|
10 |
Antophill,
Sion, Chembur
|
Central
|
8 |
| |
|
11 |
Dadar,
Matunga, Lalbaug, Lower Parel
|
Cental
|
15 |
| |
|
12 |
Virar
|
Western
|
11 |
| |
|
13 |
Dahisar,
Miraroad
|
Western |
7 |
| |
|
14 |
Bhayender
|
Western |
8 |
| |
|
15 |
Kandivli
- Borivli (East)
|
Western |
4 |
| |
|
16 |
Kandivli
- West
|
Western |
2 |
| |
|
17 |
Malad
|
Western |
4 |
| |
|
18 |
Goregaon
|
Western |
6 |
| |
|
19 |
Andheri
Jogeshwari
|
Western |
31 |
| |
|
20 |
Andheri
(W)
|
Western |
21 |
| |
|
21 |
Vile-Parle
|
Western |
6 |
| |
|
22 |
Santacruz
|
Western |
28 |
| |
|
23 |
Bandra, Khar
|
Western |
7 |
| |
|
24 |
Girgaon/Tardeo
Opera H
|
Western |
36 |
| |
|
25 |
Mahim/South
Bombay
|
Western |
1 |
| |
|
26 |
Dombivli
|
Western |
20 |
| |
|
27 |
Kurla, Wadala
|
Western |
3 |
| |
|
28 |
Mumbra/Airoli/Kalwa
|
Western |
1 |
| |
|
29 |
Borivli-West
|
Western |
21 |
| |
|
30 |
Colaba, Fort,
Cuff P. Byculla
|
South Bombay
|
10 |
| |
|
31 |
Ghatkopar (W)
and Kurla
|
Central |
33 |
| |
|
32 |
Panvel, Nerul,
Kopra, Kalamboli
|
New Bombay
|
18 |
| |
|
33 |
Pedder Road,
Breach Candy,
|
South Bombay
|
27 |
| |
|
34 |
Jogeshwari
|
Western |
6 |
| |
|
35 |
Goregaon Malad
East
|
Western |
4 |
|
| |
|
OS |
Outstation
|
Labs located
outside |
17 |
|
|
TABLE
6
Zonewise incidence - positive |
|
| Test |
Total
+ve Sample |
Zone
code |
Zone
Name |
Zone
Desc |
Samples |
|
| Leptospira
- IgM |
481 |
007 |
Direct |
Direct |
21 |
|
| |
|
1 |
Marine
lines to Colaba (Ajay)
|
South
Bombay |
3 |
| |
|
2 |
Thane
West
|
Central
|
43 |
| |
|
3 |
New
Bombay Nerul Govandi
|
Central
|
98 |
| |
|
4 |
Ulhasnagar
Ambernath Bada
|
Central
|
6 |
| |
|
5 |
Kalyan
|
Cental
|
15 |
| |
|
6 |
Thane
— East
|
Central
|
32 |
| |
|
7 |
Mulund
|
Central
|
71 |
| |
|
8 |
Bhandup,
Vikroli, Kanjurmarg
|
Cental
|
38 |
| |
|
9 |
Ghatkopar
|
Central
|
77 |
| |
|
10 |
Antophill,
Sion, Chembur
|
Central
|
24 |
| |
|
11 |
Dadar,
Matunga, Lalbaug, Lower Parel
|
Cental
|
69 |
| |
|
12 |
Virar
|
Western
|
3 |
| |
|
13 |
Dahisar,
Miraroad
|
Western |
13 |
| |
|
14 |
Bhayender
|
Western |
3 |
| |
|
15 |
Kandivli
- Borivli (East)
|
Western |
23 |
| |
|
16 |
Kandivli
- West
|
Western |
13 |
| |
|
17 |
Malad
|
Western |
17 |
| |
|
18 |
Goregaon
|
Western |
37 |
| |
|
19 |
Andheri
Jogeshwari
|
Western |
85 |
| |
|
20 |
Andheri
(W)
|
Western |
39 |
| |
|
21 |
Vile-Parle
|
Western |
6 |
| |
|
22 |
Santacruz
|
Western |
28 |
| |
|
23 |
Bandra, Khar
|
Western |
17 |
| |
|
24 |
Girgaon/Tardeo
Opera H
|
Western |
53 |
| |
|
25 |
Mahim/South
Bombay
|
Western |
5 |
| |
|
26 |
Dombivli
|
Western |
29 |
| |
|
27 |
Kurla, Wadala
|
Western |
8 |
| |
|
28 |
Mumbra/Airoli/Kalwa
|
Western |
3 |
| |
|
29 |
Borivli-West
|
Western |
57 |
| |
|
30 |
Colaba, Fort,
Cuff P. Byculla
|
South Bombay
|
5 |
| |
|
31 |
Ghatkopar (W)
and Kurla
|
Central |
30 |
| |
|
32 |
Panvel, Nerul,
Kopra, Kalamboli
|
New Bombay
|
94 |
| |
|
33 |
Pedder Road,
Breach Candy,
|
South Bombay
|
79 |
| |
|
34 |
Jogeshwari
|
Western |
6 |
| |
|
35 |
Goregaon Malad
East
|
Western |
36 |
|
| |
|
OS |
Outstation
|
Labs located
outside |
61 |
|
|
Discussion
Dengue is a deadly virus, which is found in many parts of the world. Patients
of dengue having haemorrhagic variety, if diagnosed in time, and then treated
in an intensive care unit, the mortality rate can be reduced to even 1%. Leptospirosis
is due to leptospira-spirochaete. In the past, it was thought that this disease
is uncommon and occurs only in sewage workers or workers coming in contact
with rats. Now we know that leptospira are often transmitted to humans by
the ingestion of food and drink contaminated by the urine of the reservoir
animal.
Our results show that both the illnesses are not uncommon in Mumbai and suburbs.
1335 blood samples were positive for dengue IgM antibodies. Elisa test for
dengue IgM is very helpful, though not diagnostic in the evaluation of the
cause of fever. Out of these, 606 blood samples tested strongly positive.
Regarding leptospirosis, though it was found to be not as common as dengue,
we found leptospira IgM antibodies in 516 blood samples. In 91 patients, the
test was strongly positive.
Table 4 shows that out of 129 patients, who were also referred for urine test
for leptospira, this test was positive, only in 18 patients. Similarly, out
of 31 patients referred for urine and serum leptospira, only 5 tested positive
for both.
Though demonstration of leptospira by dark field examination is very specific
and diagnostic, unfortunately, there is a lot of observer error and it depends
on the person conducting the test. Neither do many doctors ask for urine and
blood tests for dark field examination for spirochaetes.
Therefore, all over the world and in all textbooks, serological tests like
IgM test for antibodies for leptospira have been recommended as one of the
best investigations for diagnosis of leptospirosis. The sensitivity reported
is around 93% or more. Regarding the diagnosis of Dengue, although the presence
of virus in the blood would be the final word in the diagnosis, in practice,
demonstration of the Dengue IgM antibodies is enough for diagnosis, since
the demonstration of the virus is extremely difficult.
Our experience in the above cases has brought out the following facts, which
may be helpful to clinicians:-
1. Both the illnesses are quite common in Mumbai city as well as the suburbs
unlike the experience in other Indian cities1,2
2. Although the mosquitoes (responsible for transmitting dengue fever) and
the leptospira are thought to be much more in suburbs and New Bombay as compared
to Mumbai, it is interesting to note that both the diseases were as common
in South Mumbai (‘D’ ward, the most aristocratic area of Bombay,
which includes Pedder Road and Breach Candy). Even at present, many authorities
are still under the false impression that the disease occurs in slum areas
because of poor sanitation, open drainage and low socio-economic strata.1
3. What has been observed by us and perhaps reported for the first time in
world literature is that we found 104 blood samples, where Elisa test for
IgM antibodies was positive, for both the illnesses. The fact that the clinicians
sent 733 samples for both the illnesses shows that clinically, they could
not differentiate between the two illnesses.
Although in world literature, the sensitivity of both the tests has been shown
to be more than 93%, from our results, it appears that the specificity of
this test is much poorer and the test can now be compared to a test like IHa
test for amoebiasis (Indirect haemagglutination test).
Talking about the sensitivity of the Elisa test, even in patients, who test
weakly positive and are suffering from the above illnesses, it will be found
that after a week, the blood sample becomes strongly positive. Thus even a
weakly positive test is important. However, many weakly positive tests could
be due to cross reactivity and thus falsely positive.
But what is more important to note is that in the absence of demonstration
of the virus or leptospira or PCR, these tests are not 100% diagnostic. At
present, this test is very easy to perform and is a very good routine test
to screen off the above two illnesses. With the sensitivity of this test being
so high, a negative test will certainly help the family physician to exclude
these illnesses and remove the panic caused in the minds of relatives of patients,
who have recently been reading so much about these illnesses in the newspapers
- indeed, the illnesses which are deadly!
What is the likely explanation of the above cross reactivity? A possible explanation
is that when a patient suffers from one of these two infections, IgM antibodies
are formed, which could remain in the blood for a long time. The second possibility
is the poor specificity of the reagents used.
SUMMARY
Perhaps for the first time in the world literature, we have observed cross
reactivity in blood samples which tested positive for leptospira IgM and Dengue
IgM antibodies.
REFERENCES
1. Kaur IR, Sachdeva R, Arora V, Talwar V. Preliminary Survey of Leptospirosis
amongst febrile patients from Urban Slums of East Delhi. JAPI 2003; 51 : 249.
2. Sandhya A Kamath, Shashank R Joshi. Re-emerging of infections in Urban
India - Focus Leptospirosis. JAPI 2003; 51 : 247.
LOW-DOSE BUDESONIDE FOR ASTHMA
Romain Pauwels and colleagues report results from a study in which patients
with mild persistent asthma for less than 2 years, and not taking a glucocorticoid
regularly, were given low-dose budesonide or placebo for 3 years. The study
was randomised, double-blind, and large, with over 7000 patients from 32 countries.
The investigators found a reduction in exacerbations and need for oral and
systemic steroids in the budesonide group and an improvement in asthma control.
The study has strengths and weaknesses. Strengths include the large size,
and the pragmatic design means that it is looking at the effectiveness of
the intervention and the findings should be generalisable. Weaknesses include
the high number of dropouts.
The other interesting outcome is that there was a reduction in growth in children
taking budesonide, of 0.43 cm a year. The reduction was similar in young children
taking 200 µg daily or older children taking 400 µg daily. Final
height is unlikely to be affected with these small doses but it is a timely
reminder that doses of budesonide as low as 200 µg daily have measurable
systemic effects. Higher doses will inevitably have greater effects and optimising
the dose is clearly important and highlighted in the new asthma guidelines.
Anne E Tattersfiled, Tim W Harrison, Lancet; March, 2003; 29 : 1066-67.
