Analisis Penyakit Diare, Kecacingan, Kolera, Hepatitis E, Tifus
Analisis Penyakit Diare, Kecacingan, Kolera, Hepatitis E, Tifus
Disusun Oleh:
Copyright © 2013 Bezatu Mengistie et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
prioritizing interventions based on context would be and were fluent speakers of Affan Oromo collected the
useful to prevent deaths from diarrhea [12]. In Ethiopia, data. The data collection was supervised by 3 supervisors
despite the high prevalence of the disease, reports from at the center. Their role was to daily check the consis-
population-based studies are sparse. The study would be tency and completeness of the collected questionnaires
helpful in planning and implementation of prevention and re-interview randomly selected 5% of the households
strategies at the community level. Thus, the objective of to check the data quality. Trained data clerks double en-
this study was to assess the prevalence of diarrhea and tered the data using EpiData 3.1 software.
associated factors among children of age under five. The primary outcome variable was the occurrence of
diarrhea in the 2-week period preceding data collection.
2. METHODS The independent variables included socio-economic
(residence, family size, caregiver’s age, occupation,
The study was conducted in Kersa Demographic Sur- educational status, parental age, occupation, educational
veillance and Health Research Center (KDS-HRC) field status, number of children under 5 years of age in the
site, located in Eastern Ethiopia in January 2011. The household and wealth), environmental (the availability of
study site is approximately 482 kilometers from Addis hand washing facility, latrine, type of and distance from
Ababa, and it is divided into 2 urban and 10 rural kebeles water source, refuse and stool disposal) and behavioral
(the smallest administrative unit in Ethiopia), with total and child-related (child feeding practice, measles vacci-
population of 55,394 residents. Agriculture is the main nation, age and gender of the child) factors.
source of the district’s livelihood. Health services in the In this study, diarrhea was defined as the passage of
district are provided by six health centers and28 health three or more loose stools over 24 hours period or more
posts. At the kebele level, health care is delivered by frequently than normal for a child [16]. Water from pro-
extension workers who are assigned to render health ser- tected springs and/or wells, from pipe and from distribu-
vices at the local level [13]. tion post was considered as improved source [17]. Dis-
The sample size was calculated using the formula for posal of child’s stool was considered proper if the stool
estimation of single proportion [14], n = Z2*P(1 - P)/r2. was put into the latrine or buried. The economic status of
Where: Z value is 1.96: P is the prevalence of diarrhea the households was categorized into poor, middle and
among children under-five years old that was assumed to better off using wealth index, which was calculated from
be 18% [15]; and r is the margin error of estimation that the households’ assets using principal component analy-
was assumed to be 2% (0.02). This provided a sample sis [18].
size of 1417 children. To account for predicted 5% non- Descriptive statistics were used to summarize the study
response rate, the final sample was 1488 children. variables. Logistic regression analysis was performed
Households with at least one child under 5years of age separately for three variable blocks estimated the effect
were eligible for the study. Study participants were se- socio-economic, environmental, and behavioral and child
lected using a simple random sampling technique from a related factors. The final model estimated the overall
sampling registry obtained from Kersa Demographic effect of the three blocks of variables. All models used
Surveillance and Health Research Center (KDS-HRC) simultaneous entry procedure to select the significant
registration book. For households with two or more chil- determinants and adjusted for confounding factors. All
dren under 5 year of age, the index child was selected by data were analyzed using SPSS v.16 statistical software
a lottery method. (IBM SPSS, Almaden, NY, US).
Data were collected using questionnaire tested previ- To reduce excessive number of variables and resulting
ously and administered by an interviewer and the obser- instability of the model, only variables with significance
vational check list. The questionnaire was prepared P < 0.1 in the bivariate analysis were considered for in-
based on the Multiple Indicator Cluster Survey (MICS), clusion in the multivariable analysis. Variables with P <
Demographic and Health Survey (DHS) and World 0.05 in the multivariable analysis were considered sig-
Health Organization (WHO) core questionnaires related nificant. Multi-colinearity of variables was assessed by
to diarrhea. The questionnaire was written in English, calculating Variance Inflation Factor (VIF).
translated into Affan Oromo (local language), and then The study was approved by the Ethic Committee at the
translated back into English to assure its accuracy. The College of Health and Medical Sciences of Haramaya
respondents were primarily mothers of eligible children University. Mothers or caregivers of children were in-
under 5 years of age, but in the absence of the mother, formed about the study and its objectives before enroll-
the next primary caregiver was interviewed. ment. A written informed consent was obtained from the
Thirteen individuals who were trained, and experi- mother or caregiver of each participating child. All col-
enced in the KDS-HRC questionnaire administration, lected records were kept confidential.
Table 1. Socio-economic determinants of diarrhea among children under 5 years of age in Kersa District, Eastern Ethiopia, 2011.
Residence
Urban 27 188 1
Age of mother/caregiver
>34 46 157 1
Education of mother/caregiver
Occupation of mother/caregiver
Other 10 38 1
Education of father
≤4 94 398 1
Table 2. Environmental exposure variables associated with diarrhea among children under 5 years of age in Kersa district, Eastern
Ethiopia, 2011.
Availability of latrine
Yes 68 325 1
Yes 40 254 1
Refuse disposal
lack of hand washing facility, rural residence, and num- facilities had 1.92 times higher odds of having diarrhea
ber of siblings under 5 years in a household and age of compared to children in the households with no hand
the child. More specifically, children in the households washing facility(OR = 1.92, 95% CI 1.29 - 2.86) (Table 4).
who open dumped refuse around the house had 2.22
times higher odds of having diarrhea compared to chil- 4. DISCUSSION
dren in the households who used a waste disposal pit
(OR = 2.22, 95% CI 1.2 - 4.03). The odds of diarrhea was This study investigated the prevalence and socio-
1.74 times higher in children from the households with economic, environmental and behavioral risk factors of
two or more siblings compared to children in the house- diarrhea morbidity in children <5 years old in Eastern
holds with only one sibling (OR = 1.74, 95% CI 1.33 - Ethiopia. The two-week prevalence of diarrhea among the
2.28). Children in the households without hand washing children was 22.5% (95% CI: 20.3 - 24.6). The occurrence
Table 3. Behavioral, child and care related risk factors for diarrhea among children under 5 years of age, Kersa District, Eastern
Ethiopia, 2011.
No 159 438 1
≥1 year 74 197 1
No 123 461 1
No 277 926 1
Child sex
*Measles vaccination is calculated for children 9 months and above; *bottle feeding and breast feeding is calculated for children < 2 years of age.
of diarrhea was positively associated with rural residence, criterion in our study is comparable with studies con-
aged 6 to 23 months, open dumping of refuse around the ducted in Western Ethiopia [5], Egypt [19] and India
house, lack of hand washing facility and presence two or [20]. Such high rate of childhood diarrhea, despite con-
more children under <5 years old in the household. siderable improvements in water sources and sanitation
The two-week period of diarrhea occurrence used as a facilities, indicates the need for more attention.
Table 4. Multivariable analysis of risk factors of diarrhea among children under 5 years of age in Kersa district, Eastern Ethiopia,
2011.
Model I Model II Model III Final model
Risk factors
AOR (95% CI) AOR (95% CI) AOR (95% CI) AOR (95% CI)
Area of residence
Urban 1 1
Rural 2.15(1.35 - 3.43)* 1.81(1.12 - 3.31)*
Education mother/caretaker
No formal education 1.14(0.76 - 1.69) 1.23(0.79 - 1.92)
Primary and above 1 1
Family size
≤4 1 1
>4 1.30(0.98 - 1.71) 1.13(0.84 - 1.51)
Availability of latrine facility
Yes 1 1
No 1.13(0.77 - 1.67) 1.14(0.75 - 1.73)
Availability of hand washing facility
Yes 1 1
*
No 1.80(1.22 - 2.66) 1.92(1.29 - 2.86)*
Main source of domestic water 1 1
Improved
Unimproved 1.35(1.02 - 1.80)* 1.16(0.86 - 1.55)
Time to fetch water (round trip)
< 15 minutes 1 1
15 - 30 minutes 1.03(0.75 - 1.40) 1.02(0.72 - 1.44)
More than 30 minutes 1.06(0.74 - 1.51) 1.04(0.71 - 1.51)
Refuse disposal
Waste pit/burning 1 1
Open dumping 2.68(1.51 - 4.79)* 2.22(1.20 - 4.03)*
Used for manure 1.22(0.87 - 1.72) 1.12(0.77 - 1.60)
Child stool disposal
Proper 1 1
Improper 1.23(0.88 - 1.70) 1.29(0.92 - 1.81)
Number of sleeping rooms
One 1.43(0.88 - 1.70) 1.40(0.91 - 2.20)
Two or more 1 1
Number of children under 5 in the household
One 1 1
The importance of refuse in transmitting diarrhea cial support. We are also thankful for study participants, data collectors
pathogens has been documented [21]. In our study, open and supervisors for their devotion and full participation.
disposal of refuse around the house was an independent
risk factor for diarrhea. This is in agreement with other
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Abstract
Cholera is one of the oldest and best understood endemic diseases. An actual bacterial enteric
disease, it is characterized in its severe form by sudden onset, profuse painless watery stools (rice-
water stool), nausea and profuse vomiting early in the course of illness. Endemic and pandemics
are strongly linked to the consumption of unsafe water, poor hygiene, poor sanitation and crowded
living conditions. A rapid survey was conducted for the outbreak investigation on August 4, 2008.
The objectives were to investigate the outbreak, risk factors for cholera and recommend control
measures immediately. Questionnaire based random convenient sample based investigative study.
60 families were contacted by the public health students. Approximate 300 individuals were screened
for cholera cases. Simultaneously six water samples were also collected from the contacted family.
Microbiological test for Vibrio cholera and E. coli was conducted. Randomly six water samples
were collected from the Rajive colony. Microbiological test for Vibrio cholera and E. coli was con-
ducted from the department of Microbiology, PU. Vibrio cholera and E. coli were found absent, in
all the samples. One sample was found positive for unidentified bacteria.
Keywords
Cholera, Slum
1. Introduction
Cholera has been present in India since ancient times. During the 19th century, several pandemics of cholera ori-
ginated from India and spread to western countries. Currently the seventh pandemic which began in 1961 in In-
donesia is still continuing. It has involved more than 80 countries in Asia, Africa and Europe.
Cholera is both an epidemic and endemic disease. The epidemicity and endemictiy of a disease will depend
on Characteristics of the agent, and those of the system. Characteristics of the agent which influence its distribu-
*
Corresponding author.
How to cite this paper: Kumar, M. and Sharma, V.L. (2014) Outbreak Investigation of Cholera in a Slum of Northern India.
Open Journal of Epidemiology, 4, 243-247. http://dx.doi.org/10.4236/ojepi.2014.44031
M. Kumar, V. L. Sharma
tion include its ability to survive in a given environment, its virulence, the average number of organisms re-
quired to cause infection, etc. Characteristics of the system which affect the distribution of the agent include the
number of susceptible, and the opportunities it provides for transmission of the infection. Global experience has
shown that the introduction of cholera into any country cannot be prevented, but cholera can create a problem
only in areas where sanitation is defective.
Epidemics of cholera are characteristically abrupt and often create an acute public health problem. They have
a high potential to spread fast and cause death. Often-times, by the time control measures are instituted the epi-
demic has already reached its peak and is waning. Thus, cholera epidemic in a community is self-limiting. It
tends to decline after reaching its peak. This is attributed to the acquisition of temporary immunity, as well as
due to the occurrence of a large number of sub clinical cases.
The practical successes of anticontagionists were not limited to their victories over quarantines. Their opera-
tions against “filth” increased greatly their prestige. While it was difficult for the contagionists to prove that a
respective epidemic would have been even worse without quarantines; health improvements after removal of
“filth” seemed to be causally related to the latter action. Barcelona and Alicante did not experience further yel-
low fever epidemics after such campaigns in 1827, respectively 1804. The General Board of Health could point
in the cholera of 1848-1849 to the immunity of its cleaned “model houses” [1].
Peter Baldwin seeks to challenge the widely held, reductionist belief that “it was not the nature of the disease
which specified how it would be prevented and limited, but the kind of political regime under epidemic attack”.
The more interesting question, and one that Baldwin also poses but answers less satisfactorily, is whether these
dynamics determined the nature of the political systems themselves. He coins the appropriate term “neoquaran-
tinist” to describe the panoply of measures that served to control epidemiological outbreaks as opposed to pre-
venting their occurrence altogether. The emergence of these adaptive strategies is crucial to Baldwin’s interpre-
tation of the post-cholera period, and one cannot dispute the emphasis he places on them [2].
By the end of the 19th century, cholera epidemics no longer appeared in Europe and North America. The rea-
sons for this are uncertain, but standards of living had risen and many communities had made major changes in
sanitation practices and established permanent boards of health. As part of the transformation to the germ theory,
medical thought had changed in many ways as well. In 1831, most physicians believed cholera to be a nonspe-
cific, noncontagious miasmatic condition that favored the morally and physically predisposed. By the end of the
19th century, although the miasmatic interpretation still had influence, cholera was primarily understood to be a
specific contagious disease caused by a particular microscopic organism [3].
Ideas relating sickness to personal morality have long been important in European and American thought. In
the Judeo-Christian tradition, sickness has often been seen as divine punishment for sin. Cures for sexually
transmitted diseases, including syphilis, have been criticized in the belief that cures would encourage immoral
behavior. Moral and ethical issues associated with sex, food, drink, work, and emotions have also been con-
nected with the possibility of contracting or spreading disease [4].
Until Robert Koch identified the cholera bacillus in 1883; science continued to favor anticontagionism. Lead-
ing anticontagionists or contingent contagionists included Max von Pettenkofer and South wood Smith. Ac-
cording to the contingent contagionist perspective, cholera could be contagious, but only under particular cir-
cumstances [5]. The existence of the cholera bacillus did not necessarily prove cholera’s contagiousness either;
some argued that the bacillus was the product of the disease, not its cause. Another issue was how to explain the
existence of healthy carriers—people who had the cholera bacillus in their bodies but who were not sick. In
practice, public health measures often involved a blend of contagionist and anticontagionist views.
Cholera was the classic epidemic disease of the nineteenth century, as the plague had been for the fourteenth.
Its defeat was a reflection not only of progress in medical knowledge but of enduring changes in American so-
cial thought. Rosenberg has focused his study on New York City, the most highly developed center of this new
society. Carefully documented, full of descriptive detail, yet written with an urgent sense of the drama of the
epidemic years, this narrative is as absorbing for general audiences as it is for the medical historian. In a new
Afterword, Rosenberg discusses changes in historical method and concerns since the original publication of The
Cholera Years [6] [7].
Epidemic of cholera are frequent, striking adults as well as children. Epidemiological studies have shown that
cholera is responsible for about 5 - 10 per cent of all acute diarrhea cases in non epidemic situation. Global ex-
perience of the current pandemic has shown that cholera can get introduced into any country but can create
244
M. Kumar, V. L. Sharma
problem only in areas where other acute enteric infections are endemic, i.e. where sanitation is defective.
Although cholera occurs from time to time in Chandigarh slums, and in Tricity, Large number of reports
started appearing in July, 2008 from areas in and around Chandigarh. To investigate the suspected epidemic, we
have conducted a rapid survey for this outbreak investigation on August, 4, 2008.
2. Methodology
In July 2008, outbreaks of Cholera illness were reported from Rajive colony, Panchkula. This provided a chal-
lenge for the centre for public health of Panjab University, Chandigarh to identify risk factors and network with
resources available in the Panchkula for outbreak response. The objectives were to investigate the outbreak, risk
factors for cholera and recommend control measures immediately.
The investigation team was from centre for public health of Panjab University, Chandigarh. The team identi-
fied part of total cases that occurred in this colony by house-to-house survey. Risk factors were assessed by us-
ing a questionnaire. Laboratory investigations for microbiological test of water samples were done from the de-
partment of microbiology, Panjab University, Chandigarh.
A cross-sectional study was conducted by using random sampling method in a sample size of 300 individuals.
Self structured questionnaire regarding sanitation and hygiene, quality of water used for drinking and domestic
purposes was collected. About 60 families were contacted by the public health team. Approximate 300 individu-
als were screened for cholera cases. Simultaneously six water samples were also collected from the contacted
family. Microbiological test for Vibrio cholera and E. coli was conducted.
It can be concluded that poor sanitary and unhygienic conditions may be responsible for the Cholera cases
occurred in rainy season in of July, 2008.
3. Results
Table 1, shows that almost equal numbers of cases were observed from both sex. More cases were reported
from the age group 20 - 60 years. More males were affected in <20 years of age groups as compared. And only
two female cases were reported from the >60 years age group.
According to Table 2, Out of 17 cases, 10 cases were from conformed and suspected category. Equal num-
bers of cases were reported for conformed and suspected diagnoses from males and females.
Randomly six water samples were collected from the Rajive colony. Microbiological test for Vibrio cholera
and E. coli was conducted from the department of Microbiology, Panjab University, Chandigarh. Vibrio cho-
lera and E. coli were found absent, in all the samples. One sample was found positive for unidentified bacte-
ria.
<20 years 3 1 4
20 - 60 years 6 5 11
>60 0 2 2
Total 9 8 17
Conformed 2 3 5
Suspected 2 3 5
Not conformed 4 3 7
Total 8 9 17
245
M. Kumar, V. L. Sharma
4. Discussion
The city of Hamburg was hit by one of the greatest urban disasters of the century: a cholera epidemic that within
six weeks left ten thousand people dead and many more suffering the appalling symptoms of this terrible disease.
Drawing on a mass of detailed source material, this book presents a graphic portrayal of a great European city in
the throes of a major social and political crisis [8]. Cholera is entirely multiform, as are typhoid fever, pneumo-
nia, cerebrospinal meningitis and all infectious diseases without exception [9].
Despite the continued discussion about the cause of cholera, over the course of the 19th century the actual
treatment of the disease did not change much. Patients with families were cared for at home. Physicians, when
called, would use such characteristic treatments as bleeding or opium. Homeopathic methods were popular
among the middle and upper classes, as were other eclectic treatments, and all manner of dietary and hygie-
nic regimens were promoted in newspapers and books. Those without families might find themselves in charity
hospitals, which could become grim places indeed during an epidemic. Preachers gave sermons on the meaning
of cholera for both individuals and society. Riots ensued due to popular revolt against mass burials [10].
As part of the transformation to the germ theory, medical thought had changed in many ways as well. In 1831,
most physicians believed cholera to be a nonspecific, noncontagious miasmatic condition that favored the mo-
rally and physically predisposed [11].
The main symptom of cholera is diarrhea. Cases range from symptom less to severe infections. The majority of
infections are mild or asymptomatic. Typical cases are characterized by the sudden onset of profuse, effortless,
watery diarrhea followed by vomiting, rapid dehydration, muscular craps and suppression of urine. Unless there
is rapid replacement of fluid and electrolytes, the case fatality may be as high as 30 to 40 per cent. The village
leaders helped the investigation team in instituting standard hygienic measures for controlling the outbreak im-
mediately
Vibrio transmission is readily possible in a community with poor environmental sanitation. The environmen-
tal factor of importance includes contaminated water and food. Flies may carry V. cholerae. Numerous social
factors have also been responsible for the endemicity of cholera in India. These comprise certain human habit
favoring water and soil pollution, low standards of personal hygiene, lack of education and poor quality of life.
Transmission occurs from man to man via faecally contaminated waste: Uncontrolled water sources such as
well, lakes ponds, streams and rivers pose a great threat, Contaminated food and drinks: Ingestion of contami-
nated food and drinks have been associated with outbreaks of cholera. Bottle-feeding could be significant risk
factor for infants. Fruits and vegetables washed with contaminated water can be a source of infection. After
preparation, cooked food maybe contaminated through contaminated hands and flies. There is growing opinion
that complex interaction of contaminated food, water and environment rather than through public drinking water
supplies and direct contact: In developing countries a considerable proportion of cases may result from second-
ary transmission i.e. person to person transmission through contaminated fingers while carelessly handling ex-
creta and vomit of patients. Incubation period is from few hours up to 5 days, but commonly 1 - 2 days.
Leakages in water pipes coupled with poor environmental sanitation were identified as reasons for contamina-
tion of drinking water. Health education, immediate repair of leaking pipes and chlorination of water supply led
to an early control of the outbreak.
5. Conclusion
It can be concluded that poor sanitary and unhygienic conditions may be responsible for the Cholera cases oc-
curred in rainy season in of July, 2008.
6. Recommendations
Taking measure given below can minimize the risk of an outbreak of cholera and its spread. There are no other
alternative for the control of outbreak of Cholera.
1) Provision of safe water;
2) Adopting safe practices in food handling;
3) Sanitary disposal of human waste;
4) Personal and domestic hygienic practices;
5) Particular attention should be given in the pre-monsoon periods before the expected seasonal increase of wa-
246
M. Kumar, V. L. Sharma
ter-borne diseases: however these measures are expected to be in place round the year;
6) Arrange random checks for water quality for coliform organisms;
7) Ensure that the health personnel are adequately trained in oral rehyderation therapy and that recommended
guidelines are followed in hospitals.
The above steps are required both as long term measure to prevent Cholera, as well as measures to be taken in
focal area where an outbreak is anticipated. Community participation is essential to prevent an outbreak so that
safe practices are followed for storing water and for food handling.
Acknowledgements
We are thankful to the Centre for Public Health and Department of Microbiology, Panjab University for their
indispensable assistance.
References
[1] Ackerknecht, E.H. (1948) Anticontagionism between 1821 and 1867. Bulletin of the History of Medicine, 22, 562-593.
[2] Baldwin, P. (1999) Contagion and the State in Europe, 1830-1930. Cambridge University Press, Cambridge.
http://dx.doi.org/10.1017/CBO9780511497544
[3] Briggs, A. (1961) Cholera and Society in the Nineteenth Century. Past and Present, 19, 76-96.
http://dx.doi.org/10.1093/past/19.1.76
[4] Delaporte, F. (1986) Disease and Civilization: The Cholera in Paris, 1832. MIT Press, Cambridge, MA, and London.
[5] Howard-Jones, N. (1975) The Scientific Background of the International Sanitary Conferences, 1851-1938. World
Health Organization, Geneva.
[6] Pelling, M. (1978) Cholera, Fever and English Medicine, 1825-1865. Oxford University Press, New York.
[7] Rosenberg, C.E. The Cholera Years: The United States in 1832, 1849, and 1866. Chicago and London, University of
Chicago Press, 1962, 1987.
[8] Evans, R. (1987) Death in Hamburg: Society and Politics in the Cholera Years, 1830-1910. Clarendon Press, Oxford.
[9] Frieden, N. (1977) The Russian Cholera Epidemic, 1892-93, and Medical Professionalization. Journal of Social Histo-
ry, 10, 538-559. http://dx.doi.org/10.1353/jsh/10.4.538
[10] Arnold, D. (1986) Cholera and Colonialism in British India. Past and Present, 113, 118-151.
http://dx.doi.org/10.1093/past/113.1.118
[11] Leiker, J. and Powers, R. (1998) Cholera among the Plains Indians: Perceptions, Causes, Consequences. The Western
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247
Asian Pac J Trop Dis 2015; 5(3): 175-180 175
Document heading doi: 10.1016/S2222-1808(14)60648-4 襃 2015 by the Asian Pacific Journal of Tropical Disease. All rights reserved.
Peer reviewer Helminthiasis is the most common infection caused by worms that is contaminant to human body
Prof. Ravi U. Mane, Assistant Professor, parts. Normally, the worms live in the gastrointestinal tract, liver and other organs. The currently
K.S.S. College of Pharmacy, Shikrapur, available anthelmintic drugs, including albendazole, mebendazole, thiabendazole, niridazole,
Dist. Pune, Maharashtra, India. dietylcarbamazine, ivermectin, praziquantel, are widely used to control helminthiasis. But
Tel: +918483925816 these drugs have serious drawbacks such as hepatotoxicity, loss of appetite, dizziness, nausea,
E-mail: maneravi13@gmail.com vomiting, abdominal pain, headache and diarrhea. Thus, it is necessary to look for more effective
anthelmintic drugs with the minimum side effects. Eighty percent of the world’s population relies
Comments on traditional medicines and plant extracts and the active constituents are used to meet people’s
T his is a good study in which the primary health care needs. This review focuses on helminthiasis and the role of traditional plants
authors have compiled the information in the treatment of helminthiasis.
about helminthiasis and medicinal
plants with anthelmintic effect. All the
information will help researchers to
explore its scientific evidence in the
prospect studies. KEYWORDS
Details on Page 178 Anthelmintics, Cysts, Helminthiasis, Medicinal plants, Nematodes
4.1. Direct damage caused by worms Technical limitations of currently available diagnostic
methods are the most important problems in the control
T he most evident forms of direct damage are those of helminthiasis. L acking of standard clinical tests
resulting from the blockage of internal organs or from the encourages extensive invasion and poses a hindrance to
effects of pressure exerted by growing parasites (Figure 1). health managements. For basic diagnosis of helminths
Physically blockage of intestine due to large nematodes infection, the specific helminths can be identified from
( Ascaris ) or tapeworms ( Taenia, Diphyllobothrium ) the faeces and their eggs microscopically examined
that produced the formation of granulomas around and established using fecal egg count method. T his
schistosome eggs and the blockage of blood flow through is commonly useful for most species, particularly in
the liver occured, which leads to pathological changes. veterinary investigations[6]. A range of diagnostic tools
C ysts of the tapeworm ( Echinococcus multilocularis ) currently available is (Figure 3): 1) Parasitological tests,
develop in the liver, brain, lungs or other parts of body the parasites are identified microscopically; 2) Serological
cavities can lead to unusal enlargement, organ metastasis assays, the parasite-specific antibodies are detected in
and cause necrosis due to pressure exerted by cysts[5]. serum samples; 3) Antigen tests, a parasite biomarker is
Mahesh Bandappa Manke et al./Asian Pac J Trop Dis 2015; 5(3): 175-180
177
detected; 4) Molecular diagnosis, the parasite nucleic acid patients. As a result, the young patients suffer from growth
is detected; and 5) Other specific tools for detection in the retardation, diminished physical fitness, and impairment in
intermediate hosts[6,7]. However, there are certain limitations memory and cognition[10].
such as the failure to identification of mixed infections and
the technique is extremely incorrect and unpredictable for
schistosomes and soil-transmitted helminths[8]. 7. Therapy for helminthiasis
Identification of parasite
Parasitological tests Anthelmintic are drugs that act either locally to expel
microscopically.
worms from the gastrointestinal tract or systemically to
eradicate adult helminthes or developmental forms that
Detection of parasite-
Serological assays specific antibodies in serum invade organs and tissues[11]. An anthelminthic drug can act
samples. by causing paralysis of the worm, or by damaging its cuticle,
which lead to partial digestion or rejection by immune
Detection of parasite biomarker. mechanisms. Anthelminthic drugs can also interfere with
Antigen tests
the metabolism of the worm, and since the metabolic
requirements of these parasites vary greatly from one species
Detection of parasite nucleic
Molecular diagnosis acid.
to another, drugs that highly effective against one type of
worm but be ineffective against others[3]. Anthelmintic drugs
with their proper mechanism of actions are given in Table
Detection in the intermediate 1[12].
Other specific tests hosts.
6. Clinical features of helminthiasis Most of the existing anthelminthic drugs produce side effects
such as abdominal pain, loss of appetite, nausea, vomiting,
These features are depending on the helminth species, headache and diarrhea. Mebendazole is a well tolerated drug.
intensity of infection, and host age. Taenia solium can However, gastrointestinal side-effects, dizziness have been
cause not only neurocysticercosis but also mass lesions noted in few patients. Also prolonged use in hydrated or in
in brain. C hronic infection with Schistosoma causes cysticercosis, causes headache, fever, alopecia, jaundice
granulomas, fibrosis, and inflammation of the spleen and and neutropenia[13]. In order to eliminate the harmful side-
liver. Echinococcus granulosis ingested eggs can cause effects of these synthetic anthelmintic drugs, it is important
life-threatening anaphylaxis if antigens are released for us to promote the studies of traditionally used anthelmintic
from the cysts. Hookworm and schistosomiasis can infect plants which will lead to the development of new anthelmintic
pregnant women, cause neonatal prematurity and increase substances with ease of availability and lesser side-effects[14].
maternal morbidity and mortality[9]. Intestinal worms and As per World Health Organization, 80% world’s population
schistosomes infection are observed in children at school relies on traditional medicines to meet their primary health
age or younger as compared with any other age group care needs, most types of which use remedies from plants.
Table 1
Anthelmintic drugs with their mechanism of actions.
Drug Mechanism of action
Albendazole is thought to act against nematodes by inhibiting microtubule synthesis. It also has larvicidal effects in hydatid disease,
Albendazole
cysticercosis, ascariasis, and hookworm infection and ovicidal effects in ascariasis, ancylostomiasis, and trichuriasis.
Mebendazole probably acts by inhibiting microtubule synthesis; the parent drug appears to be the active form. Efficacy of the drug varies with gastrointestinal
Mebendazole
transit time, with intensity of infection, and perhaps with the strain of parasite. The drug kills hookworm, Ascaris, and Trichuris eggs.
Thiabendazole Thiabendazole is thought to act against nematodes by inhibiting microtubule synthesis.
Diethylcarbamazine Diethylcarbamazine citrate immobilizes microfilariae and alters their surface structure, displacing them from tissues and making them more
citrate susceptible to destruction by host defense mechanisms. The mode of action against adult worms is unknown.
Ivermectin appears to paralyze nematodes and arthropods by intensifying GABA-mediated transmission of signals in peripheral nerves. It is
Ivermectin
microfilaricidal. It does not effectively kill adult worms but blocks the release of microfilariae for some months after therapy.
The mode of action is thought to be related to cholinesterase inhibition. This inhibition temporarily paralyzes the adult worms, resulting in their
Metrifonate
shift from the bladder venous plexus to small arterioles of the lungs, where they are trapped, encased by the immune system, and die.
Niclosamide Adult worms are rapidly killed, presumably due to the inhibition of oxidative phosphorylation or stimulation of ATPase activity.
The mechanism of action is unknown. Contraction and paralysis of the worms results in detachment from terminal venules in the mesentery
Oxamniquine
and transit to the liver, where many die; surviving females return to the mesenteric vessels but cease to lay eggs.
It reversibly inhibits neuromuscular transmission in the worm, probably by acting like GABA, the inhibitory neurotransmitter on GABA-gated
Piperazine
Clˉ channels in nematode muscle.
Praziquantel Praziquantel appears to increase the permeability of trematode and cestode cell membranes to calcium, resulting in paralysis, dislodgement, and death.
The drug is a neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinesterase and results in paralysis, which
Pyrantel pamoate
is followed by expulsion of worms.
178 Mahesh Bandappa Manke et al./Asian Pac J Trop Dis 2015; 5(3): 175-180
Even the modern pharmacopoeia still contains at least 25% Conflict of interest statement
of drug derived from plants and many others which are
semi-synthetic, built on prototype compounds isolated We declare that we have no conflict of interest.
from plants[15]. The phytoconstituents showing anthelmintic
effect includes alkaloids, saponins, polyphenols, tannins,
etc. Alkaloids suppress the transfer of sucrose from stomach Acknowledgements
to small intestine, diminish the support of glucose to the
helminths, and act on CNS causing paralysis. Saponins possess Authors are thankful to Prof. S. G. Gattani, Director,
vacuolization and disintegration of teguments. Polyphenols and S chool of P harmacy, SRTM U niversity, N anded for his
tannins increase the supply of digestible proteins by animals valuable guidance. This work was supported by Swami
via forming protein complexes in rumen, interfere with energy Ramanand Teerth Marathwada University, Nanded (431606),
generation by uncoupling oxidative phosphorylation, cause Maharashtra, India (Grant Ref. No. Acctts/Budget/2012-
a decrease in gastrointestinal metabolism which leads to 13 / 2169 - 2209 . )
as a part of research project for partial
paralysis and death of helminths[16]. Medicinal plants list with fulfillment master degree in pharmacy.
proven anthelmintic effects are compiled in Table 2.
Table 2
Medicinal plants with anthelmintic potential. Comments
Plant name Family Part of the plant used Reference
Achyranthes aspera Amaranthaceae Stem [17] Background
Aerva lanata Amaranthaceae Aerial parts [18]
Helminth infections have severe consequences for the
Alstonia boonei Apocynaceae Bark [19]
Annona sqamosa Annonaceae Leaves [20]
health of millions of people worldwide. The synthetic drugs
Baliospermum montanum Euphorbiaceae Root [21] used in the treatment of helminthiasis can cause various
Bambusa vulgaris Bambusoideae Leaves [22] side effects, therefore, to overcome these traditional
Barleria buxifolia Acanthaceae Leaves [23] drug therapies have mainly preferred. The authors have
Cucurbitaceae Leaves [24]
compiled information about helminthiasis and medicinal
Benincasa hispida
Borassus flabellifer Palmae Leaves [25]
Capparis zeylanica Cappardiaceae Root [26] plants for its treatment.
Cassia auriculata Ceasalpinaceae Leaves [27]
Croton bonplandianium Euphorbiaceae Leaves [28] Research frontiers
Rutaceae Leaves [29]
The aim of this review article is to compile the entire
Citrus medica
Clerodendrum viscosum Verbenaceae Leaves [30]
Cocos nucifera Palmae Fruit [31] information of helminthiasis and the role of traditional
Coldenia Procumbens Boraginaceae Aerial parts [32] plants in the treatment of helminthiasis.
Coleus aromaticus Lamiaceae Root [33] Related reports
Cotyledon orbiculata Crassulaceae Shoots [34]
The authors have summarized the whole
Curcuma amada Zingiberaceae Rhizome [35]
Diplazium esculentum Athyriaceae Rhizome [36]
pathophysiological information about helminthiasis and
Drypetes sepiaria Euphorbiaceae Leaves [37] medicinal plants used in the treatment of helminthiasis.
Ficus bengalensis Moraceae Fruit [38]
Flacourtiaceae Leaves [39]
Flacourtia sepiaria Innovations & breakthroughs
Gymnema sylvestre Asclepiadaceae Leaves [40]
Hedychium spichatum Zingiberaceae Rhizome [41]
T his review article is very important to promote the
Helicteres isora Sterculiaceae Fruit [42] studies of traditionally used anthelmintic plants which will
Heliotropium indicum Boraginaceae Leaves [43] lead to the development of new anthelmintic substances
Hermannia depressa Malvaceae Shoots [34] with ease of availability and lesser side-effects.
Jasminum mesnyi Oleaceae Leaves [44]
Juglans regia Juglandaceae Stem bark [45]
Leea asiatica Vitaceae Leaves [46] Applications
Leonotis nepetiifolia Lamiaceae Leaves [47] T his review article has been found out to ba a new
Luffa cylindrica Cucurbitaceae Leaves [48] prospect in the treatment of helminthiasis with the help of
Bignoniceae Bark [49]
Millingtonia hortensis
Mimuosops elengi Sapotaceae Root and bark [37,50]
herbal drugs.
Murraya koenigii Rutacae Root [51]
Nicotiana glauca Solanaceae Shoots [34] Peer review
Oenothera rosea Onagraceae Stem and root [52] This is a good study in which the authors have compiled
Rubiaceae Leaves [53]
Paederia foetida
Pajanelia longifolia Bignoniaceae Bark [54]
the information about helminthiasis and medicinal
Portulaca oleracea Portulacaceae Leaves [55] plants with anthelmintic effect. All the information will
Saraca indica Leguminosae Leaves [56] help researchers to explore its scientific evidence in the
Spermacoce ocymoides rubiaceae Leaves [57] prospect studies.
Tamarindus indica Caesalpiniaceae Bark [58]
Tephrosia purpurea Fabaceae Leaves [59]
Terminalia arjuna Combretaceae Bark [60]
Uncaria gambier Rubiaceae Leaves [61] References
Vernonia amygdalina Asteraceae Leaves [19]
Zingiber zerumbet Zingiberaceae Rhizome [41] [1] B undy DA . I mmunoepidemiology of intestinal helminthic
Ziziphus mauritiana Rhamnaceae Leaves [62]
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J. Biomedical Science and Engineering,
http://www.scirp.org/journal/jbise
2018, Vol. 11, (No. 10), pp: 275-288
ABSTRACT
Hepatitis E caused by the Hepatitis E Virus (HEV) is a liver disease resulting in over 20
million cases every year. Hepatitis E is now considered by some scientists as an emerging
issue as HEV is not only prevalent in developing countries but is increasingly detected in
industrialized nations. In this paper, we try to provide evidence for this notion and what
actions may need to be implemented to prevent further spreading of HEV. The prevalence
of HEV, including its distinct genotype distribution in different geographic regions (in-
cluding both developing countries and industrialized countries) will be discussed; further
discussions of HEV treatments will include the availability and the mechanism of HEV vac-
cines and antiviral treatments used to treat and contain the disease. Additionally, the pre-
vention and spreading of Hepatitis E disease will be discussed in the later section of the pa-
per. With the presentation of HEV transmission route, infection regions, and treatment, we
aim to raise the awareness of the general public toward this liver disease and discuss
whether the high prevalence disease is an emerging disease worldwide. According to the
data we collected, the rate of HEV infection is high and shows a trend of increasing, which
leads to our conclusion and proves our hypothesis that Hepatitis E is a re-emerging disease.
1. INTRODUCTION
In 1978, in the Kashmir Valley of India, an unprecedented outbreak of a water-borne disease swept
around the area and resulted in over 52,000 infected cases, including 1700 deaths, raising the attention of
Figure 1. Proposed Life Cycle of HEV. Step a: HEV attaches to cell surface via HSPGs or HSC70 and
then enters the cell through unknown receptor. Step b: HEV penetrates the cell membrane and en-
ters the cell. HSPGs and HSC70 may be involved in the process. Step c: the positive-sense genomic
viral RNA serves as the template of translation of ORF1 proteins. Step d: The viral RdRp synthesizes
an intermediate, replicative negative-sense RNA. Step e: transcription of viral RNA. Step f: ORF2
and ORF 3 are translated. Step g: assembly of HEV virus. Step h: the nascent virus is transported to
the cell membrane. Step i: the virus is released from the infected cell (Dianjun Cao, et al. 2012) [10].
Figure 2. Rate of infection of HEV in different regions of India (Jain P., et al. 2013) [19].
that 82.49% of the investigated population are willing to pay for such vaccines [29]. This indicates a great
prospect of this vaccine in high risk areas.
Practicality of Implementing the HEV Vaccine in Industrialized Countries
On the bright side, the prevalence of such vaccine is shown to be practical, especially in highly in-
3.3. Treatments
Studies have shown that pregnant women and those who are immunocompromised, usually those
who received organ-transplantation, are the most vulnerable to HEV infection. Unfortunately, they are
also the ones who are not able to receive existing treatments, such as ribavirin (RBV) or interferons (IFN),
since RBV is teratogenic and IFNs can lead to graft rejection [42]. Thus, alternatives to these drugs need to
be developed.
The most common way of treating HEV infection is by using the antiviral therapy, which includes the
usage of RBV or IFNs [4]. IFNs are cytokines induced by the immune system usually in response to infec-
tion [43]. There are generally three classes of IFNs, type I, II and III. In this case, type I IFN, specifically a
subtype called IFNα is used against HEV. IFNα was shown effective in treating Hepatitis E (research
showed that 95% of HEV was eliminated in the observed patient) [44]. To increase the half-life of ex-
ogenously administered IFN, a pegylated form (pegIFNα) has been developed which is highly effective in
abrogating HEV (100% in the sixth month) [45]. More specifically, before the patients have intake the
RBV, they should first wait for a few months no matter whether their immunological risk is high or low
and then see if their bodies could immunologically fight the pathogen themselves. If their infections do not
get any better after these months, an antiviral therapy using ribavirin will be needed. Then, if further test-
ing shows that the HEV RNA still test as positive, then the ribavirin therapy should be continuously pro-
ceeded. Otherwise, the patient could continue the treatment after the HEV relapses (Figure 5).
However, treatment with IFNs has substantial side effects and can increase the risk of graft rejection
and thus their practical utility is limited. The side effects of RBV include hemolytic anemia, pulmonary
disorders, hypersensitivity and even bone marrow suppression [42]. Furthermore, cardiac patients, preg-
nant women, and their male partners should not be taking RBV, as a reverse effect in treating HEV may be
established, which further lead to side effects like hypertension, birth defects and even stillbirth [5, 47].
4. CONCLUSION
Based on our research, we can draw on the conclusion that Hepatitis E can be now identified as a
re-emerging disease and is causing millions of cases worldwide every year. HEV is highly prevalent in both
many developing and industrialized nations and significantly contributes to human morbidity and mortal-
ity world-wide. Thus, raising public awareness to the prevalence of Hepatitis E is necessary. Further, gen-
eration of novel treatments that suit all groups of people (including pregnant women) and methods of
prevention that can be applied in all countries must be a priority. As mentioned in previous sections, the
current treatment for Hepatitis E includes the use of ribavirin and interferons which have proven efficacy.
However, both treatments can cause severe side effects and cannot be employed when treating pregnant
women infected by HEV and chronic Hepatitis E in immunocompromised transplant recipients; thus,
there is an urgent need for developing novel, more tolerable treatments. Furthermore, actions in prevent-
ing HEV from spreading should be taken. Since there are great differences in the cause of HEV infections
between industrialized countries and developing countries, preventive strategies need to be considered
based on separate situations. In industrialized countries such as Germany, where HEV infections are gen-
erally caused by consumption of HEV contaminated pork and transfusion of HEV positive blood, routine
screenings for blood resource and pork can be put into application. In contrast, for those developing
countries such as India where HEV are transmitted to humans primarily through sewage contaminated
water, assurance in clean water supply should be their primary task. Global vaccination against HEV is
also a possible solution in preventing the spread of viral infections. Although effective vaccines have been
invented it is only approved for use in China but no other parts of the world. Efforts should be undertaken
to make HEV vaccines widely accessible to all parts of the world, both industrialized and developing
countries, under affordable costs. This would be a major tool for containing the spread of HEV and pre-
venting the severe and sometimes fatal disease.
ACKNOWLEDGEMENTS
Special thanks to Professor Alexander Ploss from Princeton University for the academic support of
this article and to the CIS program for offering this opportunity of studying and doing research upon this
subject.
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T
YPHOID FEVER, A FOOD- AND WA-
phoid cases, 24 confirmed paratyphoid cases, and 289 control patients with fever but
terborne disease caused by Sal- without Salmonella bacteremia were interviewed, plus 378 randomly selected com-
monella enterica serotype typhi munity controls.
(S typhi), is a serious public
Main Outcome Measures Blood culture–confirmed typhoid or paratyphoid fe-
health problem in developing coun-
ver; risk factors for both diseases.
tries that claims 600000 lives every year.1
Paratyphoid fever, caused by Salmo- Results In 1019 fever patients we identified 88 (9%) Salmonella typhi and 26 (3%)
Salmonella paratyphi A infections. Paratyphoid fever among cases was indepen-
nella paratyphi A, B, or C, has a disease
dently associated with consumption of food from street vendors (comparison with com-
presentation similar to that of typhoid munity controls: odds ratio [OR], 3.34; 95% confidence interval [CI], 1.41-7.91; with
fever, but its incidence is reportedly fever controls: OR, 5.17; 95% CI, 2.12-12.60) and flooding (comparison with com-
about one tenth that of typhoid (ratio, munity controls: OR, 4.52; 95% CI, 1.90-10.73; with fever controls: OR, 3.25; 95%
1:10-20).2,3 In developing countries the CI, 1.31-8.02). By contrast, independent risk factors for typhoid fever using the com-
identification of risk factors and rel- munity control group were mostly related to the household, ie, to recent typhoid fe-
evant route of transmission for a dis- ver in the household (OR, 2.38; 95% CI, 1.03-5.48); no use of soap for handwashing
ease such as typhoid fever is essential for (OR, 1.91; 95% CI, 1.06-3.46); sharing food from the same plate (OR, 1.93; 95% CI,
the development of rational control strat- 1.10-3.37), and no toilet in the household (OR, 2.20; 95% CI, 1.06-4.55). Also, ty-
phoid fever was associated with young age in years (OR, 0.96; 95% CI, 0.94-0.98).
egies. Resources could consequently be
In comparison with fever controls, risk factors for typhoid fever were use of ice cubes
allocated to where they count most, eg, (OR, 2.27; 95% CI, 1.31-3.93) and female sex (OR, 1.79; 95% CI, 1.04-3.06). Fecal
to the construction or expansion of contamination of drinking water was not associated with typhoid or paratyphoid fe-
water distribution networks or sewage ver. We did not detect fecal carriers among food handlers in the households.
systems, chlorination of drinking wa- Conclusions In Jakarta, typhoid and paratyphoid fever are associated with distinct
ter, ensurance of food safety, hygiene routes of transmission, with the risk factors for disease either mainly within the house-
education, mass vaccination cam- hold (typhoid) or outside the household (paratyphoid).
paigns, and/or the identification of car- JAMA. 2004;291:2607-2615 www.jama.com
riers within or outside the households
of patients. of bacteria is required for infection than Author Affiliations: Department of Infectious Dis-
eases, Leiden University Medical Center, Leiden, the
Risk factors for typhoid fever have in typhoid fever; consequently, food is Netherlands (Drs Vollaard, Visser, and van Dissel); De-
been identified in several epidemio- implicated as the major vehicle for partment of Biology, Medical Faculty (Dr Ali), Depart-
ment of Internal Medicine (Dr Widjaja), and Center
logic studies suggesting either water- transmission of paratyphoid fever, since for Health Research (Dr Surjadi), Atma Jaya Catholic
borne 4 - 8 or foodborne transmis- Salmonella bacteria can multiply in University, Jakarta, Indonesia; and Institute for Inter-
national Health, University Medical Center Nijme-
sion.7,9-11 Whether these factors coincide food.12 Comparison of the transmis- gen, Nijmegen, the Netherlands (Dr van Asten).
with those for paratyphoid fever has not sion of both diseases is becoming in- Corresponding Author: Jaap T. van Dissel, MD, PhD,
Department of Infectious Diseases, C5-P, Leiden Uni-
been determined. The assumption is creasingly relevant, because recent re- versity Medical Center, PO Box 9600, 2300 RC Leiden,
that in paratyphoid fever, a higher dose ports have demonstrated an increasing the Netherlands (j.t.van_dissel@lumc.nl).
©2004 American Medical Association. All rights reserved. (Reprinted) JAMA, June 2, 2004—Vol 291, No. 21 2607
u nt
Blood cultures of patients with non- a participant in the 12 months preced- tericidal effect of chlorine during trans-
enteric fever showed either no growth ing the interview. Intrahousehold food port was neutralized by 0.1 mL of 10%
or bacteria other than S typhi or S para- handlers were defined as individuals sodium thiosulphate. Water samples
typhi as cause of fever. Malaria could preparing meals for cases or controls were examined for total and fecal co-
be excluded in the differential diagno- 3 or more times a week. A single stool liforms by use of most probable num-
sis of prolonged fever, because trans- sample of 2 g was collected from all ber method.15 Fecal contamination was
mission does not occur in Jakarta. Ev- cases, controls, and their intrahouse- defined as a most probable number in-
ery second consecutive patient with hold food handlers in a vial with Cary- dex for fecal coliforms of 1⁄100 mL or
nonenteric fever was selected as a fe- Blair transport medium and samples greater.
ver control and visited. Also, during the were processed within 24 hours after
surveillance, community controls were collection. Water samples of 150 mL di- Statistical Methods
randomly selected within a random rectly from the source of running drink- Data from the questionnaires were en-
household in every third rukun tet- ing water were collected in the house- tered twice using EpiInfo 6.04b soft-
angga (ie, the smallest administrative holds of 62 typhoid and 20 paratyphoid ware (US Centers for Disease Control
unit of 40-60 area households) of a total cases, 341 community controls, and 233 and Prevention, Atlanta, Ga), vali-
of 1140 rukun tetanggas. When a com- fever controls using World Health Or- dated, and imported into SPSS version
munity control reported fever in the 30 ganization guidelines.15 11.5 (SPSS Inc, Chicago, Ill) for statis-
days preceding the interview or re- tical analysis. After the first 3 months of
fused participation, the house on alter- Laboratory Methods surveillance, an interim analysis was per-
nating sides of the initially selected Blood culture vials from outpatient fa- formed and the needed sample size was
household was approached. The selec- cilities were transported on the day of calculated; a minimum sample size of 80
tion of both groups of controls was collection to Mitra Internasional, one of enteric fever cases (assuming 4 times as
nonmatched for age, sex, or neighbor- the participating private hospitals with many fever controls) was required to de-
hood (ie, residence in 1 of the 8 sub- a microbiology laboratory certified by the tect significant associations (P⬍.05) be-
districts of Jatinegara) to limit selec- International Organization for Standard- tween key exposure variables and out-
tion bias and prevent overmatching. ization. Blood cultures were incubated come, with a power of 0.80. Normally
Four controls from both groups for for up to 7 days. Samples demonstrat- and nonnormally distributed numeri-
every case of enteric fever were se- ing growth were plated on blood agar cal variables were analyzed using t tests
lected to increase statistical power. medium. Salmonella typhi or S para- and Mann-Whitney U tests, respec-
typhi A were identified by use of agglu- tively. Measures for association were ex-
Household Visits tination antisera (Polyvalent, D, Vi, H, pressed as odds ratios (ORs) for dis-
and Sample Collection and Paratyphi A; Murex Biotech Ltd, ease with their 95% confidence intervals
Cases and controls were interviewed by Dartford, England) and biochemical tests (CIs) for categorical variables. To con-
trained medical school graduates, us- (Microbact; Medvet Diagnostics, Ad- trol for confounding, a multivariate
ing a standardized questionnaire that elaide, Australia). Susceptibility against analysis was performed using logistic re-
included the known risk factors from chloramphenicol, ampicillin, cotrimoxa- gression with a forward likelihood ra-
previous studies and questions from a zole, and ciprofloxacine was tested by tio test with the significantly associ-
questionnaire that was used in a simi- disk diffusion on Mueller-Hinton agar. ated variables from the bivariate analysis
lar risk factor study, which had been lo- Stool samples were cultured for Salmo- and potential confounders (eg, age,
cally tested and validated.6 Written in- nella bacteria using selenite enrich- sex, income, and neighborhood resi-
formed consent was provided by all ment broth (Oxoid Ltd, Hampshire, dence).16 Sex and income were also in-
participants at the household visit. To England). Suspected colonies as iden- cluded in the bivariate analysis; age and
prevent the overrepresentation of mul- tified by visual inspection were plated neighborhood residence were not. Effect
tiple-case households, only 1 patient on xylose-lysine-desoxycholate agar and modification by interaction of age, sex,
(ie, the first reported case or fever con- Salmonella-Shigella agar, and on triple or income was tested, but these terms
trol) per household was interviewed. If sugar iron agar, SIM (sulphide and in- were not significantly associated and did
cases or controls were younger than 13 dole production and motility) me- not change the ORs of associated vari-
years, the mother or guardian was in- dium, and Simmons citrate (Oxoid). ables. The attributable risk of each in-
terviewed. No time frame for hygiene Bacterial identification was identical to dependently associated variable from the
behavior and food habits was men- that for bacteria from blood cultures. multivariate analysis was calculated.17
tioned, because it aimed at the descrip- Samples from the sources of drink-
tion of usual practice. A household was ing water were transported on ice and RESULTS
defined as a dwelling whose inhabit- processed within 6 hours after collec- Surveillance Study
ants ate from the same pot. Flooding was tion at the Nusantara Water Centre.15 During the study period 1019 consecu-
defined as inundation of the house of In samples from piped water the bac- tive patients with fever lasting 3 or more
©2004 American Medical Association. All rights reserved. (Reprinted) JAMA, June 2, 2004—Vol 291, No. 21 2609
Demographic Data From phoid fever. Among the 2 control ver: crowding (⬎6 household mem-
the Visited Cases and Controls groups, fever controls were more of- bers) and recent typhoid fever of house-
The median age of the typhoid cases was ten male, from a lower income group, hold contacts (TABLE 2). The association
16 (range, 3-57) years; of paratyphoid observed poorer handwashing hy- of recent typhoid fever of household
cases, 22 (range, 4-59) years; of com- giene, had fewer toilets and connec- contacts and typhoid fever also re-
munity controls, 27 (range, 1-80) years; tions to the water mains in their houses, mained significant in a subgroup of
and of fever controls, 20 (range, 1-75) shared food more frequently, were more households with more than 6 house-
years (TABLE 1). Typhoid and paraty- likely to consume iced drinks, and were hold members: from the 34 typhoid
phoid fever cases and fever controls more likely to report flooding than were cases, 8 (24%) reported recent typhoid
were significantly younger than the community controls (Table 1). fever in a household contact, whereas
community controls (P⬍.01). The age In addition, for all interviewed par- from 137 community controls, 9 (7%)
of patients with typhoid fever did not ticipants, low income was signifi- did (OR, 4.38; 95% CI, 1.54-12.40). In
differ significantly from that of those cantly associated with purchasing food the comparison with community con-
with paratyphoid fever (P = .12). Fever from street vendors (OR, 1.58; 95% CI, trols, other significantly associated risk
controls were significantly more often 1.03-2.41). When ice cubes were used, factors for typhoid fever were no use of
of male sex than were community con- these were purchased from ice ven- soap for handwashing, no toilet in the
trols (P=.003 by 2 test) and typhoid dors by equal proportions in the groups: household, and flooding. With respect
cases (P = .03). No significant differ- 41 (69%) patients with typhoid or para- to eating habits, typhoid was not signifi-
ences in the sex ratio were found when typhoid fever, 107 (61%) community cantly associated with eating food from
typhoid or paratyphoid cases were com- controls, and 93 (71%) fever controls street vendors, but a significant associa-
pared with community controls. Com- (P = .12). tion was found with consuming iced
pared with the number of community drinks, use of ice cubes, and sharing food
controls per subdistrict, who had been Bivariate Analysis from the same plate. Sharing of food oc-
included proportionally to the size of Risk Factors for Typhoid Fever. Bi- curred mostly with household con-
the population, in 1 subdistrict pro- variate analysis of risk factors compar- tacts: 84% (26/31) of typhoid and para-
portionally more typhoid cases than ing typhoid cases with community con- typhoid cases and 84% (85/101) of
community controls were enrolled trols showed the following significantly community controls and in lower fre-
(P = .07), whereas in another subdis- associated risk factors for typhoid fe- quencies in all groups at work or school.
trict more patients with paratyphoid fe-
ver were enrolled (P = .05). Within the Table 1. Risk Factors for Typhoid and Paratyphoid Fever in Jakarta
group of patients with enteric fever it- Cases, No. (%) Controls, No. (%)
self, no significant overrepresentation
of any subdistrict was found in the com- Typhoid Fever Paratyphoid Fever Community Fever
Risk Factor (n = 69) (n = 24) (n = 378) (n = 289)
parison of patients with typhoid and Age, median (range), y 16 (3-57) 22 (4-59) 27 (1-80) 20 (1-75)
paratyphoid fever (P = .37) Female sex 40 (58) 9 (38) 211 (56) 126 (44)
Low family income* 40 (58) 9 (38) 182 (48) 174 (60)
Risk Factors for Typhoid
Household size, median (range)† 6 (3-200) 5 (2-8) 6 (1-50) 6 (1-20)
and Paratyphoid Fever
Crowding‡ 34 (49) 8 (33) 137 (36) 101 (35)
Risk factors for typhoid and para- Recent typhoid fever 11 (16) 3 (13) 23 (6) 27 (9)
typhoid fever in comparison with com- in the household
munity and fever controls are shown in No use of soap for handwashing 49 (71) 15 (63) 214 (57) 183 (63)
Table 1. Compared with paratyphoid No toilet in household 15 (22) 5 (21) 33 (9) 38 (13)
cases the typhoid cases were more of- Eating food from street vendors 22 (32) 13 (54) 85 (23) 59 (20)
ten female, lived in more crowded con- Consumption of iced drinks 17 (25) 5 (21) 51 (14) 62 (22)
ditions, were more frequently from a Use of ice cubes 45 (65) 14 (58) 176 (47) 131 (45)
lower income category, more fre- Sharing food from same plate 31 (45) 7 (29) 102 (27) 101 (35)
quently reported recent typhoid fever Eating with hands 33 (48) 11 (46) 164 (43) 121 (42)
among household contacts in the pre- Drinking water: piped water 7 (10) 2 (8) 77 (20) 42 (15)
ceding 12 months, used ice cubes more Fecal contamination of 30 (48) 11 (55) 192 (56) 125 (54)
drinking water source§
often, shared food more often, and ob-
Flooding 26 (38) 14 (58) 79 (21) 99 (34)
served poor handwashing hygiene. *Defined as below the median monthly income of the community controls (900 000 Rupiah [US $105]).
Flooding and eating food purchased †Includes 2 outliers: an orphanage with 200 individuals and a dormitory with 50 individuals in the typhoid cases and
community controls, respectively.
from street vendors were more fre- ‡Defined as more than the median number of household members of community controls (median, 6).
quently reported by patients with para- §Water samples obtained from 62 typhoid cases, 20 paratyphoid cases, 341 random community controls, and 233
fever controls.
typhoid fever than by those with ty-
©2004 American Medical Association. All rights reserved. (Reprinted) JAMA, June 2, 2004—Vol 291, No. 21 2611
Table 2. Bivariate Analysis of Risk Factors for Typhoid and Paratyphoid Fever in Comparison With Community Controls and Fever Controls
Odds Ratio (95% Confidence Interval)
Risk Factor Community Controls Fever Controls Community Controls Fever Controls
Female sex 1.09 (0.65-1.84) 1.78 (1.05-3.04) 0.48 (0.20-1.11) 0.78 (0.33-1.83)
Low family income 1.49 (0.88-2.50) 0.91 (0.54-1.55) 0.65 (0.28-1.51) 0.40 (0.17-0.94)
Crowding 1.71 (1.02-2.86) 1.81 (1.06-3.07) 0.88 (0.37-2.11) 0.93 (0.39-2.25)
Recent typhoid in the household 2.93 (1.36-6.32) 1.84 (0.86-3.92) 2.21 (0.61-7.94) 1.39 (0.39-4.95)
No use of soap for handwashing 1.88 (1.07-3.28) 1.42 (0.80-2.52) 1.28 (0.55-2.99) 0.97 (0.41-2.28)
No toilet in household 2.90 (1.48-5.70) 1.84 (0.94-3.57) 2.75 (0.97-7.85) 1.74 (0.61-4.93)
Eating food from street vendors 1.61 (0.92-2.83) 1.83 (1.02-3.26) 4.07 (1.76-9.42) 4.61 (1.96-10.81)
Consumption of iced drinks 2.10 (1.13-3.90) 1.20 (0.65-2.22) 1.69 (0.60-4.72) 0.96 (0.35-2.68)
Use of ice cubes 2.15 (1.26-3.68) 2.26 (1.31-3.91) 1.61 (0.67-3.71) 1.69 (0.73-3.93)
Sharing food from same plate 2.21 (1.31-3.74) 1.52 (0.89-2.59) 1.11 (0.45-2.77) 0.77 (0.31-1.91)
Drinking water: piped water 0.44 (0.19-1.01) 0.66 (0.29-1.55) 0.36 (0.08-1.54) 0.54 (0.12-2.36)
Fecal contamination of drinking water source 0.73 (0.42-1.25) 0.81 (0.46-1.42) 0.95 (0.38-2.35) 1.06 (0.42-2.64)
Flooding 2.29 (1.33-3.95) 1.16 (0.67-2.00) 5.30 (2.27-12.38) 2.69 (1.15-6.27)
Female sex was associated when ty- cantly different for typhoid or paraty- the multivariate analysis are shown
phoid cases were compared with fever phoid fever cases vs those for fever in TABLE 3.
controls, which was likely due to the controls (P = .54 and P = .90, respec- Risk Factors for Typhoid Fever. Us-
overrepresentation of males in the fe- tively, by Mann-Whitney U test) or ing the community control group, ty-
ver control group (Table 2). In the fe- community controls (P=.43 and P=.95, phoid fever continued to be indepen-
ver-control comparison crowding was respectively). All respondents re- dently associated with hygienic
associated with typhoid fever, as was ported that they boiled drinking water practices (no use of soap for handwash-
eating foods from street vendors and use before consumption and that they kept ing, sharing of food, and no toilet in the
of ice cubes. None of the hygiene- water boiling for several minutes. household) and recent intrahouse-
related risk factors (ie, no use of soap hold typhoid fever in the preceding 12
for handwashing, no toilet in the house- Food Handlers months. These are presented in order
hold) was significantly associated with A food handler was not present in all of decreasing magnitude of attribut-
typhoid in comparison with fever households of cases or controls be- able risk (Table 3). Typhoid cases were
controls. cause some cases and controls always significantly younger than commu-
Risk Factors for Paratyphoid Fever. ate outside of the household or cooked nity controls, suggesting that either ex-
In comparison with community con- their own food. No S typhi or S para- posure to S typhi or susceptibility to
trols and fever controls, paratyphoid fe- typhi A were isolated in the single stool symptomatic infection when exposed
ver among cases was significantly as- samples that could be obtained from is greater among young people.
sociated with eating foods from street 96% of the 78 food handlers of (para) Using the fever controls for compari-
vendors and flooding. Fever controls typhoid cases, 246 of the fever con- son, we identified ice cubes and fe-
had a lower family income than did pa- trols, and 298 of the community con- male sex (related to the high percent-
tients with paratyphoid fever. trols, respectively. age of male participants in the fever
control group) as independent risk
Water Examination Multivariate Analysis factors for typhoid fever. Hygiene-
During the study period, 656 samples Residence of participants in 1 of the 8 related factors were not indepen-
from the sources of running drinking subdistricts was not evaluated in the dently associated.
water of cases and controls were col- bivariate analysis, but was included in Risk Factors for Paratyphoid Fe-
lected; 358 (55%) contained fecal co- the multivariate analysis as a potential ver. In the multivariate analysis, para-
liforms (median, 30; IQR, 6-250 per 100 confounder. In this analysis, neigh- typhoid fever continued to be indepen-
mL). Fecal contamination of drinking borhood residence was not indepen- dently associated with eating foods from
water was not significantly associated dently associated with either typhoid street vendors when paratyphoid cases
with either typhoid or paratyphoid fe- fever or paratyphoid fever. The sig- were compared with both control groups
ver in comparison with both control nificant risk factors for typhoid (Table 3). Flooding also remained a sig-
groups (Table 2). Also, bacterial num- and paratyphoid fever from the bivari- nificant risk factor for paratyphoid fe-
bers in water samples were not signifi- ate analysis that were evaluated in ver. The individual contribution of eat-
2612 JAMA, June 2, 2004—Vol 291, No. 21 (Reprinted) ©2004 American Medical Association. All rights reserved.
fever controls were of a standard below febrile illnesses (OR, 1.40; 95% CI, trict neighborhood residence, this
that of community controls. In addi- 1.05-1.88). The combination of poor assumption could not be verified. Finally,
tion, partially overlapping routes of handwashing hygiene, eating with although a considerable proportion of
transmission of typhoid fever and other hands, and sharing food from the same the sources of drinking water con-
febrile illnesses could be interdepen- plate can understandably facilitate trans- tained fecal coliforms that were used as
dent and result in the demonstrated mission of typhoid, but apparently the indicator organisms, contamination itself
similar intrahousehold risk profile of ty- infective dose to allow transmission of was not associated with enteric fever.
phoid fever cases and fever controls with paratyphoid is only infrequently met. Dilution of S typhi or S paratyphi in water
similar socioeconomic characteristics. Because we observed no intrahouse- might generate too low a dose to infect
Food obtained from street vendors hold outbreaks and detected no fecal partially immune residents. More likely,
was a likely vehicle for extrahousehold carriers among the food handlers in the however, the entrenched habit of boil-
transmission of paratyphoid fever be- households of cases, intrahousehold ing drinking water from the water mains
cause it contributed significantly to person-to-person spread through or groundwater pumps explains the lack
transmission in contrast to hygiene- convalescent patients observing poor of an association between water con-
related risk factors. This is consistent hygiene seems a more likely scenario tamination and enteric fever and should
with the notion that multiplication of than transmission by chronic carriers certainly be continued to prevent pos-
paratyphoid bacteria in food is re- among food handlers in households. sible outbreaks of disease, in combina-
quired to reach a number sufficient to Apart from the above-mentioned risk tion with proper storage of boiled water
cause disease. Street vendors have only factors, some additional observations to prevent domestic contamination.
limited facilities for cooled storage of should be considered. First, the total In conclusion, the present findings
foods and for washing of hands, foods, number of interviewed patients with suggest that public health policies for
and dishes. The low hygienic stan- typhoid and paratyphoid fever in our control of typhoid and paratyphoid fe-
dards could therefore contribute not study was limited, which may have influ- ver in Jakarta should focus on hygiene
only to the transmission of paraty- enced the statistical power of the analy- education as well as monitoring of the
phoid fever but of other foodborne dis- sis, especially in small subgroups, and street-food trade, although such strat-
eases such as typhoid, as well.7,11,27-29 Due the demonstrated associations of spe- egies would have to be tested in inter-
to the Asian economic crisis starting in cific risk factors. Second, food pur- vention trials to prove their value. First,
1997, the expanding urban population chased from street vendors could be instruction on proper handwashing hy-
became even more dependent on inex- implicated as a vehicle for transmission giene using soap could reduce the over-
pensive food obtained from street ven- of typhoid as well, as shown in the bivar- all incidence of infectious diseases in
dors, which may explain the relatively iate analysis. Also, the consumption of Jakarta and especially preclude trans-
high proportion of paratyphoid fever in ice cubes obtained from street vendors mission of typhoid fever among con-
enteric fever in Jakarta. Low-income might expose clients to Salmonella bac- tacts of cases. Second, prevention of
groups more frequently ate food ob- teria because these bacteria can survive bacterial contamination of street food
tained from street vendors than did in- in ice.31 Another extrahousehold loca- and ice cubes could contribute to con-
dividuals with high income, but all in- tion of acquisition of typhoid fever could tainment of enteric fever, paratyphoid
come groups who purchase food from be public toilets, which generally lack in particular. Follow-up of enteric fe-
street vendors may be at risk. handwashing facilities. Third, there was ver cases, especially among food ven-
In contrast to the largely extra- an association between flooding and dors, should be prioritized to reduce the
household transmission of paraty- paratyphoid fever. Two hypotheses may role of transient or chronic carriers in
phoid fever, typhoid fever was more of explain this association: flooding could the foodborne transmission.
an intrahousehold affair introduced by introduce bacteria from contaminated If vaccination were to be consid-
recent typhoid cases in the house- surface water into sources of drinking ered as a means of controlling ty-
holds and facilitated by poor hand- water. However, since most cases of phoid, an individualized approach
washing hygiene and sharing of food typhoid and paratyphoid fever occurred rather than mass vaccination (ie, tar-
from the same plate, consistent with an during the dry season, flood-related geted vaccination of young household
earlier report.10 The association of poor waterborne transmission seemed not to contacts of cases) may be a cost-
handwashing hygiene and typhoid fever play a major role. Alternatively, flood- effective approach when public health
was shown before in Indonesia and ing may be an income-associated geo- resources are scarce.32 But, because of
India.6,9,11 A recent review stressed the graphic marker that coincides with the the increasing incidence of paraty-
importance of the use of soap for the distribution of carriers among food ven- phoid fever in Jakarta, as well as readily
reduction of the incidence of diarrheal dors in the area. This could also explain available antibiotic treatment and the
diseases.30 In our study we also iden- the clustering of paratyphoid fever cases potentially effective intervention of edu-
tified a significant association between in some regions, but since community cation to increase appropriate hand-
not using soap for handwashing and all controls were nonmatched for subdis- washing, mass immunization pro-
2614 JAMA, June 2, 2004—Vol 291, No. 21 (Reprinted) ©2004 American Medical Association. All rights reserved.
grams for typhoid fever in Jakarta may Administrative, technical, or material support: Vollaard, ment of Medical Statistics for critically reviewing the
Ali, Widjaja, Surjadi. document and Wil Dolmans, MD, PhD, for his help
not be appropriate at this time. Study supervision: Vollaard, Ali, Widjaja, Visser, Surjadi, in the preparatory stage of this project. We thank
van Dissel. the physicians, nurses, and technicians of the par-
Author Contributions: Dr van Dissel, as principal in- Funding/Support: This study was supported by the ticipating health centers in Jakarta for their coop-
vestigator, had full access to all of the data in this study Royal Netherlands Academy of Arts and Sciences eration: Mitra Internasional hospital and micro-
and takes full responsibility for the integrity of the data (KNAW). biology laboratory, Budhi Asih, St Carolus and
and accuracy of the data analysis. Role of the Sponsor: The Royal Netherlands Acad- Persahabatan hospital, all puskesmas in Jatinegara,
Study concept and design; critical revision of the manu- emy of Arts and Sciences had no role in the design the local private practitioners, as well as the micro-
script for important intellectual content: Vollaard, Ali, and conduct of the study; the collection, manage- biology department of Atma Jaya University Hospi-
van Asten, Widjaja, Visser, Surjadi, van Dissel. ment, analysis, and interpretation of the data; or the tal and Nusantara Water Centre, West Jakarta. This
Acquisition of data: Vollaard, Ali. preparation, review, or approval of the manuscript. study could not have been done without our
Analysis and interpretation of data: Vollaard, Ali, Acknowledgment: We thank J. P. Vandenbroucke, research assistants: Billy Hunsinger, Ferry Kandaw,
van Dissel. MD, PhD, from the Leiden University Medical Cen- Rinny Listyani, Meily, Vea Noveria, Carmelita Rid-
Drafting of the manuscript: Vollaard. tre (LUMC) Department of Clinical Epidemiology wan, Min Ali Sugiharto, Lidwina Sutikno, Mariana
Statistical expertise: Vollaard, van Asten, van Dissel. and Nico Nagelkerke, PhD, from the LUMC Depart- Tasman, and Lily Yaputra.
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©2004 American Medical Association. All rights reserved. (Reprinted) JAMA, June 2, 2004—Vol 291, No. 21 2615