A CAJM article on malnutrition in children.Investigations of the immune response have, until recently, thrown little light on the reasons for the increased severity of infections in malnourished children. It has been established that in these children levels of immunoglobulins are at least as high as in well-nourished children, which suggests that there is no defect in the humoral response (Watson and Freesmann, 1970). However, by measuring antibody production it was shown in 12 of 15 children suffering from Kwashiorkor that the injection of typhoid vaccine failed to cause a rise in antibody titre (Budiansky and da Silva, 1957), and a similar observation was made in relation to yellow fever vaccination (Katz and Brown, 1966). It is possible, therefore, that the immunoglobulins of severely malnourished children may not be fully competent and further work to clarify this is indicated

Kendall, A.C.

Nolan, R.

Central African Journal of Medicine

English

IDS OpenDocs

The Central African Journal of Medicine
Editor: | '
MICHAEL GELFAND, C.B.E., M.D., F.R.C.P.
Assistant Editor: 
JOSEPH RITCHKEN, M.D.
Volum e Eighteen 
JANUARY - DECEMBER 
1972
Sa lis b u r y R hodesia
V ol. 18 No. 4 A pril, 1972
Fig. 9—Rhodesian isolate of Hong Kong influenza.
Polym orphonuclear 
Leucocytic Activity in  
M alnourished Children
BY
A. C. KENDALL
AND
R. NOLAN
Department of Paediatrics, University of Rhodesia.
I ntroduction
Many observers have drawn attention to the in­
creased mortality in both viral and bacterial 
infections in tropical and sub-tropical countries 
and related thus not to an increased virulence of 
the organisms concerned, but to the diminished 
iresistance of the host. There can now remain 
little doubt that malnutrition plays an important 
role in this diminished resistance (Morley, 1969). 
In recent years the immune responses have been 
intensively studied, the various processes, involved 
have been described and in many instances quan­
titated. These recent advances which have been 
the subject of several reviews (Janeway, 1969), 
have shown that primary host resistance is of 
three types, humoral in which resistance to micro­
organisms is mediated by circulating immuno­
globulins, secondly the immune cellular response 
of* thymic dependant lymphocytes, and thirdly,
Now that the disease is so rare it is suggested 
that the diagnosis in every suspected case should 
be confirmed in the laboratory and instructions 
are included for the taking and submission of 
specimens.
A few examples are given of the usefulness of 
the electron microscope in the diagnosis of virus 
diseases other than smallpox, particularly diseases 
producing skin lesions in man and animals.
T h e  Central African
J ournal of Medicine
REFERENCES
Annual Reports of the Secretary for Health, Rhodesia. 
(1964-1970).
Bedson, H. S. & D umbell, K. R. (1961). J. Hyg. Camb. 
59, 457.
Cruickshank, J. G., Bedson, H. S. & Watson, D. S. 
(1966) Lancet, ii, 527.
Official Records of the World Health Organisation No. 
188 p. 15. 1970.
All electron micrographs are at a magnification of 
about 222 000 X.
_________________  V,
polymorphonuclear leucocyte activity. Isolated de­
fects of each of these systems have been described 
and studies of these patients have shown that the 
common infecting organisms may be grouped 
according to the type of immune response which 
they specifically evoke (Mudd, 1970) (see Table
I ) .
Table 1
Pathogens and Immune Response T hey 
Specifically Evoke
Primary Host Defence Pathogenic Organisms
H umoral
Pneumococcus 
H. Influenzae 
Streptococcus 
Meningococcus sp. 
Pseudomonas aeruginosa 
Hepatitis virus 
Pneumocystis carinii
Cellular
Rubeola
Varicella
Vaccinia
Cytomegalic inclusion body virus 
Mycobacterium tuberculosis 
Candida albicans 
Histoplasmosis
Polymorphonuclear
Leucocytic
Activity
Staphylococcus 
Klebsiella sp. 
Aerobacter aerogenes ■ 
Serratia marcescens 
Candida albicans 
Aspergillus 
Nocardia
73
April, 1972 POLYMORPHONUCLEAR LEUCOCYTIC ACTIVITY The Central African
Journal of Medicine
Investigations of the immune response have, 
until recently, thrown little light on the reasons 
for the increased severity of infections in mal­
nourished children. It has been established that 
in these children levels of immunoglobulins are 
at least as high as in well-nourished children, 
which suggests that there is no defect in the 
humoral response (Watson and Freesmann, 1970). 
However, by measuring antibody production it 
was shown in 12 of 15 children suffering from 
Kwashiorkor that the injection of typhoid vac­
cine failed to cause a rise in antibody titre 
(Budiansky and da Silva, 1957), and a similar 
observation was made in relation to yellow fever 
vaccination (Katz and Brown, 1966). It is pos­
sible, therefore, that the immunoglobulins of 
severely malnourished children may not be fully 
competent and further work to clarify this is in­
dicated.
There is evidence that in states of malnutrition 
the immune cellular response is deficient. Malnu­
trition diminishes resistance to tuberculosis, an 
adequate diet increases resistance (Brock, 1961). 
Tuberculin sensitivity in tuberculous patients, a 
reaotion which is also dependant on the same 
immunological response is diminished in mal­
nourished children and full sensitivity can be 
restored by a short period of high protein feeding 
(Phillips and Wharton, 1968). It has been shown 
that in Kwashiorkor there is not only a reduction 
in size of the thymus and thymic dependant 
lymphatic tissues, but also a functional depres­
sion of this system. Allogeneic skin grafts are 
rejected more slowly and the response to dinitro- 
fluorobenzene and the transformation of lympho­
cytes in response to stimulation with phytohae- 
magglutinin are both diminished (Smythe, 1970).
Bacterial infections are frequent and often fatal 
in patients suffering from Kwashiorkor. In one re­
ported series of 78 patients blood cultures were 
taken on admission. The organisms recovered 
were staphylococcus aureus on five occasions, 
salmonellae on six, paracolon and coliforms in 
three, and streptococcus oneumoniae in two 
(Smvthe and Campbell, 1959). Thus staphylo­
cocci and enterobacteriacae accounted for 14 of 
16 positive cultures and a similar pattern of in­
fecting organisms has been found by lung punc­
ture aspiration in the pneumonias of malnourished 
children (Axton). Resistance to these groups of 
organisms is dependant upon polymorphonuclear 
(P.M.N.) activity, a process which has been 
shown to be defective in the genetically deter­
mined condition, chronic granulomatous disease 
(C.G.D.) (Good, et al., 1968). Studies of patients 
with this condition have shown that the persisting
infections and the ultimate fatal outcome are due 
to an inability of the P.M.N.’s to destroy staphylo­
cocci and organisms ' of the enterobacteriacae 
group.
In comparing patients. suffering from C.G.D. 
with those suffering from Kwashiorkor not only 
are there similarities between the infecting organ­
isms, but the pulmonary infections of patients 
with C.G.D. typified by their ohronicity, tendency 
to encapsulation and enlargement of the hilar 
shadows (Wolfson, et al., 1968), are reminiscent 
of the pneumonias seen in severely malnourished 
children. These considerations suggest that 
P.M.N. activity may be defective in malnutrition! 
Studies of the way in which the P.M.N.’s destroy 
certain pathogenic bacteria have shown that two 
stages, are involved. The first is phagocytic inges­
tion, the second enzymatic'killing and digestion of 
the intracellular bacteria. Phagocytic activity of 
P.M.N.’s from malnourished persons using staphy­
lococcus albus as the tSst organism has been re­
ported as being normal ^Tejada, et al., 1964). The 
possibility remains that tjhe severity of these bac­
terial infections in malnqurished children may be 
the result of an inadequate leucocytosis or a de­
fect in bacterioidal capacity of the P.M.N.’s. A 
method has been described recently by which using 
staphylococcus aureus as a test organism the 
phagocytic and bactericidal functions of the 
P.M.N.’s can be estimated separately (Alexander, 
et al., 1968). Unfortunately, this investigation is 
difficult and complex, the author reports that he 
and his two colleagues worked on it for a year 
before reliable results were obtained. A simpler 
method suggested itself in that the P.M.N.’s of 
patients with chronic granulomatous disease show 
a constant histochemical abnormality, an inability 
to reduce tetrazolium dyes (Baehner and Nelson, 
1968). During phagocytic activity normal 
P.M.N.’s reduce nitroblue-tetrazolium to readily 
visible intracellular deposits of formazan, the 
P.M.N.’s from affected persons show only very 
slight activity in this respect. Although the rela­
tionship between the histochemical abnormality 
and the enzymatic defect is not clear the test is 
now reliably used for the diagnosis of C.G.D. 
While the tetrazolium reducing capacity of 
P.M.N.’s from patients with chronic granuloma­
tous disease is virtually absent, transient abnor­
malities of a lesser degree have been reported in 
patients on treatment with corticosteroids (Miller 
and Kaplan, 1970). The present investigation 
was undertaken to see whether similar histochemi­
cal abnormalities could be demonstrated in mal­
nutrition.
A pril, 1972 T he Central African
Journal of MedicinePOLYMORPHONUCLEAR LEUCOCYTIC ACTIVITY
Method
All specimens were processed within 30 min­
utes of collection. Using a plastic disposable 
syringe, 1 ml. of venous blood was taken, trans­
ferred to a disposable plastic tube and by gentle 
inversion mixed with 100 units of heparin. A 
specimen obtained from a normal adult was in­
cluded in each batch of tests, the results are re­
ported in Table II, but are not considered further 
in the discussion. 0.2 ml. of blood was trans­
ferred to a siliconised glass tube, an equal amount 
of nitroblue-tetrazolium solution (0.2 per cent. 
N.B.T. in physiological saline with an equal 
amount of 0.15 M phosphate buffered saline at 
pH 7.2) was added and also 0.05 ml. of a suspen­
sion of latex of particle size 0.8 microns. After 
mixing by inversion the tubes were incubated for 
30 minutes at 37 deg. C. At the end of this time 
the buffy layer which had formed was pipetted 
off, films were made, dried in air, fixed with 
methanol and stained with May-Griinwald/Giemsa 
stain. The method used was a modification of a 
technique previously described (Park, et al., 1968).
Before examining the films the slides were 
randomised and a code was allotted to each. The 
code was only broken after all the slides in each 
batch had been examined. The Boston charts 
were used to assess the percentile weight of each 
patient and the results are as plotted in Table II, 
children below and above the third percentile 
being shown separately.
This examination was carried out in four heal­
thy adults, three of whom were tested on more
than one occasion and 37 patients who were un­
selected except that they were all suffering from 
malnutrition. A specimen of blood was obtained 
from eaoh of these children as soon after admis­
sion as possible.
Results
The test has shown a very significant difference 
(.001 >  p) between the P.M.N.’s of children be­
low the third percentile by weight compared with 
those above. It will also be seen that there is a 
very wide scatter of values indicating that the 
histochemical abnormality observed although re­
lated to malnutrition is expressed only in some 
children and in these to a varying degree. The 
results, however, offer an explanation of the ob­
served susceptibility of malnourished children to 
infections with staphylococci and enterobacteria- 
cae and of the severity and resistance to therapy 
of these infections. Further work , is needed in 
order to correlate P.M.N. activity as determined 
by this test with the character and clinical course 
of any complicating infections. It is possible also 
that the test could be used as a means of identi­
fying those children who are at particular risk 
from certain bacterial infections. A further point 
concerns the therapy 'of infections in severely 
malnourished children. If as is suggested the 
bactericidal capacity of the P.M.N.’s is reduced 
in some of these children, phagocytosed bacteria 
will persist in the intracellular situation in a viable 
state, as has been shown to occur in C.G.D. These 
intracellular bacteria are protected from the action 
of penicillin, streptomycin and kanamycin since
TABLE 2
RESULTS OF THE N.B.T TEST
H E A L T H Y  A D U L TS PATIENTS BELOW 3rd. PERCENTILE
P A TIE N TS  AAOVE 
3rd. P g Q C E N TILE _
too
09
00
OS
00
79
70
09
90
PERCENTAGE 99 
O F so  
POSITIVE 
CE LLS  49 
40 
39 
30 
29 
20 
19 
10 
9 
0
• • •
•
• • • 
*•
•
* * • .
. • • •
• •
• • •
• *
• • •
•
•
••
•
• * .
••
IDENTIFICATION
NUMBERS
t 2 3 ’ 1 2 3 4 9 9  7 1 2  3 4 1 2 3 4 9 9 .7 9 0 10 11 12 13 14 19 19 17 16 10 20 21 22 33 24 29 29 27 23 20 1 2 3 4 9 0 7 6
kDULT 1 Ia d u l t  t ADULT 3 ADULT 4 PATlFNTS
75
Vol. 18 No. 4 A pril, 1972
these antibiotics do not penetrate the ceil wall of 
the P.M.N. On the other hand the cell wall does 
not exclude chloramphenicol and this antibiotic 
is therefore effective against viable intracellular 
bacteria. In treating the infections of severely 
malnourished children it may be advantageous to 
consider this property of the chosen antibiotic in 
addition to the results of sensitivity tests.
Summary
Investigations have shown an abnormality of 
enzymatic activity within the P.M.N.’s of some 
malnourished children. This offers an explanation 
of their known susceptibility to certain bacterial 
infections and of the clinical features of these 
infections.
Acknowledgments
We are very indebted to Dr. W. Castle for her 
statistical analysis of the results and to Dr. E. 
Forbes for allowing us to carry out this examina­
tion on her patients.
REFERENCES
Alexander, J. W., H egg, M., and Altemeier, W. A.
(1968). Ann. Surg., 168, 447.
Axton, J. H. M., Personal communication.
Baehner, R. L., and Nathan, D. (1968). New Eng. J. 
Med., 278, 971.
Budiansky, E., and da Silva, N. (1957). Quoted in 
Recent Advances in Human Nutrition (1961). Ed. 
Brock, p. 378. Churchill, London.
Infections Agents and Host Reactions (1970). Ed. Mudd, 
p. 105, Saunders, Philadelphia and London.
Janeway, C. A. (1966). Arch. Dis. Childh., 41, 358. 
Good, R. A., Quie, P. G., W indhorst, D. B., Page, A. R. 
R odey, G. E., W hite, J., W olfson, J . J., and H olmes,
B. H. (1968) Seminars Hemal., 5, 215.
Katz, M., and Brown, R. E. (1966). Trop. geogr. Med., 
18,125.
M iller, D. R., and K aplan, A. B. (1970). Pediatrics, 45, 
861.
Morley, D. C. (1969). Brit. med. J. 1, 297.
Park, B. H., F ikrig, S. M., and Smithwick , E. M. 
(1968). Lancet, 2, 532.
P hillips, L., and Wharton, B. (1968). Brit. med. J., 1, 
407.
Recent Advances in Human Nutrition (1961). Ed. Brock, 
p. 375, Churchill, London.
Smythe, P. M. (1970). Communication at 9th South 
African Paediatric Congress.
Smythe, P. M. and Campbell, J. A. H. (1959). S.A. 
med. J., 33, 111.
Tejada, C., Argueta, V., Sanchez, M., and Albertazzi,
C. (1964). Paediatrics, 64, 753.
Watson, C. E. and F reesman, C. (1970). Arch. Dis. 
Childh., 45, 282.
W olfson, J. J., Quie, P. G., Laxdal, S. D. and Good, 
R. A. (1968). Radiology, 91, 37.
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Polymorphonuclear Leucocytic Activity In Malnourished Children

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Polymorphonuclear Leucocytic Activity In Malnourished Children

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