ABSTRACT: We conducted a nested case-control study in 397 rural Egyptian children <36 months of age to assess the correlation between serum levels of antibodies against toxin and colonization factors (CFs) and the risk of homologous enterotoxigenic Escherichia coli (ETEC) diarrhea.
Active case detection was performed via semiweekly home visits, and blood was obtained at 3-month intervals. After each serosurvey, case subjects were selected from children experiencing a CF antigen (CFA)/I-, CFA/II-, CFA/IV-, or heat-labile enterotoxin (LT)-ETEC diarrheal episode during the subsequent 3 months. Up to 5 control subjects per case subject were selected from children who did not experience an ETEC diarrheal episode during the corresponding interval. Serum titers of immunoglobulin G antibodies against CFA/I, coli surface antigen (CS) 3, CS6, and LT were measured by enzyme-linked immunosorbant assay.
The distribution of serum titers of LT, CS3, and CS6 antibodies did not differ between the case and control subjects. For children <18 months of age, serum titers of CFA/I antibody were inversely related to the risk of CFA/I-ETEC diarrhea; reciprocal serum titers of CFA/I antibody > or =76 were associated with a 77% reduction in the odds of CFA/I-ETEC diarrhea.
Induction of reciprocal serum titers of antibodies against CFA/I within or above the 76-186 range should be further evaluated as a predictor for assessment of the ability of candidate vaccines to protect against CFA/I-ETEC diarrhea.
The Journal of Infectious Diseases 03/2005; 191(4):562-70. · 6.41 Impact Factor
ABSTRACT: Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of O antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir.
Journal of Clinical Microbiology 01/2005; 42(12):5588-95. · 4.15 Impact Factor
ABSTRACT: During the period from February 1995 to February 1998, the epidemiology of Shigella diarrhea was studied among children less than three years of age residing in Egypt's Nile Delta. Children were visited twice a week and a stool sample was collected from any of them with diarrhea. The incidence of Shigella-associated diarrhea was 0.2 episodes/child-year, with S. flexneri being the most common serogroup isolated (55% of Shigella episodes). Younger age and the warm months increased the risk of developing Shigella-associated diarrhea, while breastfeeding was protective. Children with Shigella were ill for a mean of four days and passed a mean of six stools per day. Common symptoms included fever (35%), vomiting (19%), and dehydration (16%). Dysentery, however, was unusual, occurring in only 11% of the cases. In conclusion, Shigella-associated diarrhea remains relatively common in Egyptian children and supports the need for additional control measures including vaccine development.
The American journal of tropical medicine and hygiene 10/2004; 71(3):367-72. · 2.59 Impact Factor
ABSTRACT: Comparative and trend analysis was conducted on annual prevalence of antimicrobial susceptibility among Campylobacter jejuni and Campylobacter coli recovered from rural Egyptian children from 1995 through 2000. C. jejuni and C. coli demonstrated significant decreasing trends in ciprofloxacin susceptibility over the study period (p < 0.001 for both). In general, C. coli demonstrated a higher degree of susceptibility than C. jejuni, however, there was no statistical difference (p = 0.2) comparing the linear trends over the duration of the study. There was no indication of frank macrolide (erythromycin or azithromycin) resistance among any Campylobacter. Moreover, there were statistically significant positive trends in both the MIC(50) and MIC(90) values for the erythromycin and azithromycin during the study period, suggesting a possible decreasing trend in susceptibility among Campylobacter. This study demonstrated that antimicrobial susceptibility in Campylobacter has significantly decreased from 1995 through 2000 among pediatric diarrhea cases in rural Egypt.
Diagnostic Microbiology and Infectious Disease 01/2004; 47(4):601-8. · 2.53 Impact Factor
ABSTRACT: The objective of this study was to describe a mass-immunization campaign of a locally-produced oral, killed whole-cell cholera vaccine in Hue city, Vietnam. Mass immunization with a 2-dose regimen of the vaccine was conducted in 13 communes in early 1998. The total, age- and sex-specific vaccine coverage was calculated using data from the vaccination records and the government census. The number of vaccine doses procured, administered, wasted, and left over, and the human and other resources required to prepare and conduct the vaccination campaign were systematically recorded. Government expenditure for planning, procurement, and delivery of the vaccine were documented. In total, 118,555 (79%) of the 49,557 targeted population were fully vaccinated during the mass-vaccination campaign. The total expenditure for the project was US dollar 105,447, resulting in a cost per fully-vaccinated person of US dollar 0.89. Mass immunization with this locally-produced oral, killed cholera vaccine was found to be feasible and affordable with attainment of high vaccination coverage.
Journal of Health Population and Nutrition 01/2004; 21(4):304-8. · 0.95 Impact Factor
ABSTRACT: The incidence of enterotoxigenic Escherichia coli diarrhea among Egyptian children was 1.5 episodes per child per year and accounted for 66% of all first episodes of diarrhea after birth. The incidence increased from 1.7 episodes per child per year in the first 6 months of life to 2.3 in the second 6 months and declined thereafter.
Journal of Clinical Microbiology 11/2003; 41(10):4862-4. · 4.15 Impact Factor
ABSTRACT: Demographic indicators such as fertility rates and infant mortality rates are often measured in census surveys by interviewing mothers to obtain their pregnancy histories and child deaths. The validity of such surveys depends upon accurate recall of histories, truthful reporting of events and understanding of the questions posed. To measure the reliability of maternal reporting, two census surveys conducted in a rural Egyptian population were compared. Women between 15 and 55 years of age residing in 20 villages were asked their histories of live births, stillbirths and child deaths. An identical set of questions was posed 2 years later. Twice-monthly home visits were conducted in the intervening 2-year interval to identify accurately any new births, stillbirths and deaths occurring in the population. The maternal reports from the first census were combined with the prospectively identified births, stillbirths and deaths and compared with the maternal reports from the second census. For 1502 women, the discrepancies in the total number of births, stillbirths and child deaths reported between the two surveys were 0.6%, 4% and 0.6% respectively. However, when the consistency of responses was analysed, the proportion of women with discordant responses was 10%, 6% and 7% for the same measures. These results suggest that, despite the large number of births and deaths that women may experience in developing countries, maternal interviews provide reliable responses that can be used to estimate mortality and fertility rates in settings where vital records are incomplete or unreliable.
Paediatric and Perinatal Epidemiology 05/2003; 17(2):125-31. · 2.31 Impact Factor
ABSTRACT: Hepatitis C virus (HCV) infection and schistosomiasis are major public health problems in the Nile Delta of Egypt. To control schistosomiasis, mass treatment campaigns using tartar emetic injections were conducted in the 1960s through 1980s. Evidence suggests that inadequately sterilized needles used in these campaigns contributed to the transmission of HCV in the region. To corroborate this evidence, this study evaluates whether HCV infections clustered within houses in which household members had received parenteral treatment for schistosomiasis.
A serosurvey was conducted in a village in the Nile Delta and residents were questioned about prior treatment for schistosomiasis. Sera were evaluated for the presence of antibodies to HCV. The GEE2 approach was used to test for clustering of HCV infections, where correlation of HCV infections within household members who had been treated for schistosomiasis was the parameter of interest.
A history of parenteral treatment for schistosomiasis was observed to cluster within households, OR for clustering: 2.44 (95% CI: 1.47-4.06). Overall, HCV seropositivity was 40% (321/796) and was observed to cluster within households that had members who had received parenteral treatment for schistosomiasis, OR for clustering: 1.76 (95% CI: 1.05-2.95). No such evidence for clustering was found in the remaining households.
Clustering of HCV infections and receipt of parenteral treatment for schistosomiasis within the same households provides further evidence of an association between the schistosomiasis treatment campaigns and the high HCV seroprevalence rates currently observed in the Nile delta of Egypt.
BMC Infectious Diseases 01/2003; 2:29. · 3.12 Impact Factor
ABSTRACT: Prior to the evaluation of protective efficacy, experimental vaccines conventionally undergo phase II randomized controlled clinical trials to evaluate safety and immunogenicity. Typically, an experimental vaccine is compared to another vaccine or to a placebo with respect to adverse events or immune responses, or both. Various strategies and methods are available for design and analysis of such studies. A key aspect of design is the determination of sample size. Often a sample size is chosen that gives a high probability ("power") of finding a statistically significant difference in an outcome of interest, if a difference of a specified size exists. This approach is appropriate when the primary goal of the study is to demonstrate that a difference exists between two groups or treatments. It may not, however, give adequate assurance that a confidence interval around the observed difference will be narrow enough to exclude the possibility of an unacceptably low immune response or unacceptably high adverse event frequency in recipients of the experimental vaccine. In this paper, we apply the "non-inferiority" trial design to phase II vaccine studies; that is, we design the trial to rule out a difference between the vaccine and control in immunogenicity or reactogenicity that is considered unacceptable. We also consider a setting in which the desire is to show that the difference between immune response rates for vaccine and control is greater than a specified value.
Vaccine 10/2002; 20(27-28):3364-9. · 3.77 Impact Factor
There is significant controversy about how best to control cholera epidemics
in refugee settings. Specifically, there is marked disagreement about whether
to use oral cholera vaccines in these settings, despite the improved safety
and effectiveness profiles of these vaccines.Objective.—
To determine the cost-effectiveness of alternative intervention strategies,
including vaccination, to control cholera outbreaks in sub-Saharan refugee
A cost-effectiveness analysis based on probabilities of cholera outcomes
derived from epidemiologic data compiled for refugee settings in Malawi from
1987 through 1993; data for costs were obtained from a large relief agency
that provides medical care in such settings.Setting and Participants.—
A hypothetical refugee camp with 50000 persons in sub-Saharan Africa
evaluated for a 2-year period.Interventions.—
We compared the costs and outcomes of alternative strategies in which
appropriate rehydration therapy for cholera is introduced preemptively (at
the establishment of a camp) or reactively (once an epidemic is recognized)
and in which mass immunization with oral B subunit killed whole-cell (BS-WC)
cholera vaccine is added to a rehydration program either preemptively or reactively.Main Outcome Measures.—
Cost per cholera case prevented and cost per cholera death averted.Results.—
In a situation with no available rehydration therapy suitable for the
management of severe cholera, a strategy of preemptive therapy ($320 per death
averted) costs less and is more effective than a strategy of reactive therapy
($586 per death averted). Adding vaccination to preemptive therapy is expensive:
$1745 per additional death averted for preemptive vaccination and $3833 per
additional death averted for reactive vaccination. However, if the cost of
vaccine falls below $0.22 per dose, strategies combining vaccination and preemptive
therapy become more cost-effective than therapy alone.Conclusions.—
Provision for managing cholera outbreaks at the inception of a refugee
camp (preemptive therapy) is the most cost-effective strategy for controlling
cholera outbreaks in sub-Saharan refugee settings. Should the price of BS-WC
cholera vaccine fall below $0.22 per dose, however, supplementation of preemptive
therapy with mass vaccination will become a cost-effective option.
Figures in this Article
WORLDWIDE, crowded refugee camps with contaminated water sources and
inadequate sanitation have been well described as foci for cholera outbreaks.1- 6
The rapidly growing number of refugees resulting from war, civil strife, famine,
and natural disasters is expected only to add to the number who have already
died as a consequence of such cholera epidemics. The provision of an adequate
quantity of purified water and the establishment of suitable facilities for
defecation pending appropriate sanitation systems are important measures to
help prevent outbreaks of cholera in refugee settings. Appropriate case management
with oral rehydration therapy, community outreach to improve case finding
and access to treatment, and hospital management for severe cases can reduce
the case-fatality ratio (CFR) in cholera epidemics from more than 50% to less
than 1%.4,7- 12
In the last decade, however, the CFR in cholera outbreaks in refugee settings,
even within the same country, has varied from less than 1% to as high as 25%.
Such variation is in part a consequence of the disparate availability of resources
needed to effectively manage such outbreaks.12- 13
Clearly, more effective strategies to prevent cholera are needed. At
present, use of additional interventions to assist in the control of cholera
outbreaks in refugee settings is not recommended. Mass antibiotic chemoprophylaxis
is considered ineffective and may be associated with the emergence of drug-resistant
In the past, injectable cholera vaccines have been rejected because of low
efficacy and too short a duration of protection.16
The recent availability of more efficacious oral cholera vaccines, such as
the recombinant oral B subunit killed whole-cell (rBS-WC) vaccine, its nonrecombinant
and the live attenuated CVD 103-HgR vaccine,21- 22
has led to renewed interest in vaccination to prevent outbreaks in situations
with high cholera incidence, such as refugee populations.23- 24
However, controversy surrounds the cost-effectiveness of vaccination in such
settings. To address this controversy, we report a cost-effectiveness analysis
of several alternative intervention strategies, including vaccination, to
control cholera outbreaks in sub-Saharan refugee settings.
JAMA The Journal of the American Medical Association 279(7):521-525. · 30.03 Impact Factor
ABSTRACT: Background Prevention of excessive heat loss is fundamental to survival of low birthweight (LBW) newboms. The use of infant incubators (INC) is beyond the resources of developing countries, and the space-heated room (SHR) has been the only feasible means of providing thermal protection to LBW newboms. Recently a thermostatically controlled, heated, water-filled mattress (HWM) has been developed as a potentially simpler and affordable alternative. Methods In a neonatal care ward of a referral hospital in Addis Ababa, 62 <1 week old newboms, weighing 1000–1999 g, who were well enough to breathe comfortably in room air and tolerate oral feeds, were randomly allocated to INC, HWM or SHR and followed for 3 weeks. The level of cold stress as assessed by core-to-skin temperature gradient and the rate of weight gain were the main outcome measures Results The level of cold stress was lowest in the INC, intermediate in the HWM and highest in the SHR. Relative to the INC group, the HWM group exhibited a modest increase in the occurrence of clinically important hyperthermic or hypothermlc deviations in core temperature (rate ratio (RR) = 2.3; 95% Cl: 0.9, 5.6), and the SHR displayed a definite increase (RR = 4.0; 95% Cl: 1.7, 9.3). During the first week, the rate of weight gain was highest in the INC group (3.6 g/kg/day), lowest in the SHR group (−2.3 g/kg/day, P < 0.05 versus INC) and intermediate in the HWM group (1.6 g/kg/day, P > 0.1 versus INC). Conclusion Care in the SHR produced clinically significant thermal stresses and was associated with deficient early neonatal growth, but the use of HWM may constitute a feasible and clinically acceptable alternative in providing warmth to LBW newboms during the neonatal period.