Burden of infectious diseases in South Asia
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7443.811 (Published 01 April 2004) Cite this as: BMJ 2004;328:811All rapid responses
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The disease burden due to Acute
Infectious Paediatric Diarrhoea (AIPD) is quite high in developing countries.
However, several other diseases exist as backend or front-end events of AIPD.
The disease causal chains (DiCC) are rarely studied in infectious diseases. Burden
of several infectious diseases rely on certain back events of DiCC. Front-event
measures are like pruning the branches of disease tree while back event measures
uproot the tree. The DiCC’s should be studied as a spatial epidemiological
problem for all the diseases together. The AIPD DiCC’s drawn in this note are
just to provide the model.
Mapping the risk events
(I)
“Rotavirus (Ro)” triggers “Acute infectious paediatric diarrhoea
(Da)”. “Ro” also triggers “Diabetes (Ds) [1]”, an autoimmune
disease. “Da” and “Ds” are prevented (denoted by “Da-“ and “Ds-“
respectively) in a child having “sufficient immunity (Is+)”.
“Is+” is seen in exclusively breast-fed infants. “Is+” is required to
face the “infection (In)” of “Ro” or “Pathogens
responsible for diarrhoea other than rotavirus (NRo)”.
(II)
“Marginal immunity
(Is+/-)” coupled with “In” cause successful “production of limitedenterotoxin (E+/-) [2]” due to growth of pathogen. NSP-4 protein of
rotavirus is an enterotoxin “Production of excessive enterotoxin (E)”
coupled with “marginalnervouscontrol (NC+/-) on fluid
secretion” due to the inadequacy of neurotransmitter enkephalins [3] leads to
“Da” and thereafter “Is+”.
(III)
“Immunity is impaired – or immunodeficiency
is subjected -- or immunity is lacking (IdIL)” due to “Unhygienic
conditions and malnutrition (UM)”. This is common in communities having
low socio-economic status. UM promote the chances of several other infections
and gut dysbiosis [4] that leads to both “IdIL” and “In”. “E” is the
result of combined action of “IdIL” and “In”. “E” coupled with
“NC+/-“ leads to diarrhoea. Appropriate intervention leads to complete
recovery and health.
(IV)
Enkephalin inadequacy becomes functional only when successful production
of “E” due to pathogen replication causes intracellular calcium
mobilization. Neurotransmitters Serotonin and Vasoactive Intestinal Peptide are
also involved in rotavirus diarrhoea [5]. A child having “Da” due to “E”
and “Loss of nervous control (NC-) on fluid secretion” may survive but might
have depleted vitamin A [6] and other nutrients that render it malnourished.
Such a child is susceptible to other diseases [7] and hence is termed as “vulnerable
(VDa) child due to diarrhoea”. A “VDa” child might die due to other
diseases causing “Death (DhVDa)” or lead to “IdIL” a vicious
cycle.
(V)
“Death (DhR)
of a child” could happen due to “Acute infectious (rotavirus) diarrhoea
(Da)”
(VI)
Adequacy of enkephalins could lead to “Da-“. but may not stop
replication of virus in the intestine. Replication of virus in the absence of
adequate barrier may allow the virus to cross the intestinal barrier causing
extra-intestinal complication of virus like “Ds”. Autoimmune diabetes due to
agents other than rotavirus also occurs.
(VII)
“Ds” could also occur after “Da”
List of Risk events
S. |
Abbreviation |
Brief |
Da |
Acute |
|
Da- |
Prevention |
|
DhR |
Death |
|
DhVDa |
Death |
|
Ds |
Diabetes, |
|
Ds- |
No |
|
E |
Production |
|
E+/- |
Production |
|
IdIL |
Low |
|
In |
Infection |
|
Is+ |
Sufficient |
|
Is+/- |
Marginal |
|
NC- |
Loss of |
|
NC+/- |
Marginal |
|
NRo |
Pathogens |
|
Ro |
Rotavirus |
|
UM |
Unhygienic |
|
VDa |
Vulnerable |
Disease Causal Chains (DiCC)
S. No. |
Outcome |
Back event-1 |
Back enent-2 |
Back event-3 |
Back event-4 |
Back event-5 |
1 |
Da-, Ds- |
Is+ |
|
|
|
|
|
|
In |
|
|
|
|
2a |
Is+ |
Da |
Nc+/- |
|
|
|
|
|
|
E+/- |
Is+/- |
|
|
|
|
|
|
In: Ro |
|
|
2b |
Is+ |
Da |
Nc+/- |
|
|
|
|
|
|
E+/- |
Is+/- |
|
|
|
|
|
|
In: NRo |
|
|
3 |
Da |
NC+/- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In |
UM |
|
|
4a |
DhVDa |
VDa |
Da |
NC- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In: Ro |
UM |
4b |
DhVDa |
VDa |
Da |
NC- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In: NRo |
UM |
5a |
DhR |
Da |
NC- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In: Ro |
UM |
|
5b |
DhR |
Da |
NC- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In: NRo |
UM |
|
6 |
Ds |
Da |
NC- |
|
|
|
|
|
|
E |
IdIL |
UM |
|
|
|
|
|
In: Ro |
UM |
|
7 |
Ds |
Da- |
NC+ |
|
|
|
|
|
|
IdIL |
|
|
|
Interpretation:
- Prevention of unhygienic conditions
and malnutrition is the golden rule for developing countries to prevent DiCC
3, 4a, 4b, 5a, 5b and 6. This is a back-end event giving rise to several
diseases at front-end; DiCC’s are drawn only for diseases associated with
diarrhoea pathogens.
- Effect of prevention of dysbiosis
through use of prebiotics or probiotics on enteric nervous system is a
virgin area of research. Whether nervous controls depend upon the health of
eco-organ (native gut microbiota) is yet to be investigated. Use of
probiotics [8] for treatment and lactic fermented foods [9] for prevention
of acute infectious paediatric diarrhoea is known.
- Effect of exposure to the morning
Sun thereby up-regulating the nervous controls is the virgin area of
research. Sufficiency of vitamin D [10] is expected to reduce intracellular
calcium mobilization thereby diarrhoea. Winter is a confounder of rotavirus
diarrhoea. Vitamin D deficiency is common during winter.
- Human milk
contains the following:
Antibodies-
binds to rotavirus; action similar to vaccine [11] but passive
Bifidobacteria
Growth Factor (Prebiotics)- At the back of beneficial action of bifidobacteria
[12]
Bifidobacteria-
Cytokine modulator, prevents inflammation thereby progression from “E” to
“Da and onwards” [13].
Rotavirus
disease is not characterized by inflammation. How inflammatory conditions within
the mucosa affect rotavirus diarrhoea remain largely unanswered [14].
Bifidobacteria
enhance immune-mediated protection [15] thereby down regulation of IdIL in DiCC
3, 4a, 4b, 5a, 5b and 6.
Trypsin
Inhibitor (Inhibits trypsin. Trypsin enhances rotavirus infectivity [16];
therefore trypsin inhibitor down regulates “E” in DiCC 3, 4a, 4b, 5a, 5b and
6) [17]
Lactadherin
(inhibits rotavirus binding, down regulates “E” in DiCC 3, 4a, 4b, 5a, 5b
and 6) [18]
Lactoferrin
(hindering adsorption and internalisation into cells through specific binding to
cell receptors and/or viral particles; down regulates “E” in DiCC 3, 4a, 4b,
5a, 5b and 6) [19]
Other
milk proteins [20]
Vitamin
A, D, Minerals etc and
Other
factors [21] and will prevent multiple events.
DiCC
also points out that role of human milk in nervous control of fluid secretion is
a virgin area for research.
- Effect similar to human milk may be
expected from designers food or value added functional foods like hyperimmune
animal colostrums or milks. How rotavirus vaccination of mothers or
dairy animals affects immune components of milk other than antibodies is a
virgin area for research. Several value added products could be developed
from dairy milks.
- Speaking of rotavirus vaccine
[22], it will not only prevent progression from “IdIL” to “E” in
DiCC 5a but will also prevent the same in DiCC 4a. It means rotavirus
vaccine can prevent not only deaths due to rotavirus diarrhoea but also
reduce to some extent deaths from measles or respiratory viruses. However,
it is contemporary understanding that rotavirus vaccine will not prevent
diarrhoea triggered by pathogens other than rotaviruses as shown in DiCC 4b
and 5b. Vaccine is expected to prevent “E” in DiCC 6, however, safety
test of vaccine are required as live vaccine virus itself may trigger DiCC
6. Toxoid vaccine might stop “Da” but may trigger DiCC 6. Viraemia is
common in children infected with rotavirus, which may be associated with
extra-intestinal involvement [23].
- Oral rehydration therapy
[24] will prevent progression from “Da” to “DhR” in DiCC 5a and 5b
but will not prevent progression from “Da” to “VDa” in DiCC 4a and
4b. It will also not prevent progression of “Da” to “Ds” in DiCC 6.
- The Racecadotril [25] will
prevent progression from “NC-“ to “Da” in DiCC 5a, 5b and 6 but will
not prevent progression from “Da” to “Ds” in DiCC 6.
References
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J, Guerrero ML, Chaturvedi P, Newburg SO, Scallan CD, Taylor MR, Ceriani RL,
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Competing interests:
None declared
Competing interests:
Dear Sir,
I would like to thank the BMJ for its issue dedicated to the health
of South Asia (3rd April 2004). Having spent the first half of 2004 in
northern India working as a volunteer doctor, the articles provided
valuable data to support the experiences I had. There are an estimated
576,480 child deaths per year from diarrhoea*, 64% of women in India
receive no antenatal care^, and, as stated in an earlier BMJ issue, 52% of
Indian children have stunted growth.
In some circumstances, statistics seem to understate the magnitude of
the problem. As pointed out by Zaidi et al*, laboratory confirmation by
culture of diseases such as typhoid is rarely attempted, but clinical
typhoid is seen frequently in practice. The burden of HIV in India may
also be far greater than 4.58 million persons infected*. The social
stigma associated with an HIV positive family member, and the lack of
availability or affordability of anti-retroviral therapy, leaves little
incentive to get tested for the virus.
The above appalling figures on health contrast starkly with
impression we may have of India from abroad. However, this positive image
also reflects the truth; the economy is growing rapidly, lead by the IT
sector and manufacturing, and work in an increasing number of industries
is being outsourced to India. Indeed the burgeoning middle class in India
enjoys a lifestyle and standard of healthcare comparable to developed
nations. The point often missed is that the vast majority of Indians, 700
million or so, live in rural areas, sometimes in grinding poverty, where
even the most basic amenities are still lacking.
As health in developed countries continues to improve and our
attention is increasingly turned towards the very worthy, but expensive,
treatment of chronic illnesses, the need for young doctors to spend time
working in underprivileged regions is greater than ever. The foundations
of western medicine are in the treatment of ailments that, sadly, still
exist in the developing world, and it is there that the lessons of public
health are most effectively taught. Most importantly though, in addition
to making a contribution to the health of those less fortunate, doctors,
as part of their training, ought to at least learn that this “other” world
exists.
Dr Subodh B. Joshi
MBBS (Melb), MRCP (Ed),
Royal Melbourne Hospital
Australia
*BMJ 2004;328:811-815,
^BMJ 2004;328:816-819,
BMJ 2000; 321: 809-812
Competing interests:
None declared
Competing interests: No competing interests
Re: Burden of infectious diseases in South Asia
In preparing milk for children, hygiene during handling is essential in order to prevent contamination of the milk. Bad handling can provoke diarrhea in the child. This can be avoided by complying with some measures such as:
· Washing the hands when preparing the milk
· Always using the same utensils
· After boiling milk, refresh milk rapidly in order to be able to save it as soon as possible in the refrigerator
· Cover the container of boiled milk before keeping it in the cold. This aspect is very important in order to prevent drops of water from the freezer or any other liquid falling into the milk and contaminating it.
It is better to prevent than to have to cure. Diarrhea is a very common problem in children and sometimes everything is caused by bad Hygiene when preparing foods, including milk.
Competing interests: No competing interests