Formative research and development of an evidence-based communication strategy: the introduction of Vi typhoid fever vaccine among school-aged children in Karachi, Pakistan.

The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination.

Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guérin (BCG) vaccines from different sources, Kazakhstan.

BACKGROUND: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. METHODS/FINDINGS: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. LIMITATIONS: Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. CONCLUSIONS/SIGNIFICANCE: All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration should be given to prevention effectiveness of BCG preparations.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan.

BACKGROUND: Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools in the two townships. The administrative staff was requested information on school fee, class enrolment, past history of involvement and willingness of parents to participate in a vaccination campaign. RESULTS: A total of 304,836 students were enrolled in 1,096 public, private, and religious schools (Madrasahs) of the two towns. Five percent of schools refused to participate in the school census. Twenty-five percent of schools had a total enrolment of less than 100 students whereas 3% had more than 1,000 students. Health education programs were available in less than 8% of public schools, 17% of private schools, and 14% of Madrasahs. One-quarter of public schools, 41% of private schools, and 43% of Madrasahs had previously participated in a school-based vaccination campaign. The most common vaccination campaign in which schools participated was Polio eradication program. Cost of the vaccine, side effects, and parents' lack of information were highlighted as important limiting factors by school administration for school-based immunization programs. Permission from parents, appropriateness of vaccine-related information, and involvement of teachers were considered as important factors to improve participation. CONCLUSIONS: Health education programs are not part of the regular school curriculum in developing countries including Pakistan. Many schools in the targeted townships participated in immunization activities but they were not carried out regularly. In the wake of low immunization coverage in Pakistan, schools can be used as a potential venue not only for non-EPI vaccines, but for a catch up vaccination of routine vaccines.

Influenza and bacterial pathogen coinfections in the 20th century.

To help understand the potential impact of bacterial coinfection during pandemic influenza periods, we undertook a far-reaching review of the existing literature to gain insights into the interaction of influenza and bacterial pathogens. Reports published between 1950 and 2006 were identified from scientific citation databases using standardized search terms. Study outcomes related to coinfection were subjected to a pooled analysis. Coinfection with influenza and bacterial pathogens occurred more frequently in pandemic compared with seasonal influenza periods. The most common bacterial coinfections with influenza virus were due to S. pneumoniae, H. influenzae, Staphylococcus spp., and Streptococcus spp. Of these, S. pneumoniae was the most common cause of bacterial coinfection with influenza and accounted for 40.8% and 16.6% of bacterial coinfections during pandemic and seasonal periods, respectively. These results suggest that bacterial pathogens will play a key role in many countries, as the H1N1(A) influenza pandemic moves forward. Given the role of bacterial coinfections during influenza epidemics and pandemics, the conduct of well-designed field evaluations of public health measures to reduce the burden of these common bacterial pathogens and influenza in at-risk populations is warranted.

Assessment and comparative analysis of a rapid diagnostic test (Tubex®) for the diagnosis of typhoid fever among hospitalized children in rural Tanzania.

BACKGROUND: Typhoid fever remains a significant health problem in many developing countries. A rapid test with a performance comparable to that of blood culture would be highly useful. A rapid diagnostic test for typhoid fever, Tubex®, is commercially available that uses particle separation to detect immunoglobulin M directed towards Salmonella Typhi O9 lipopolysaccharide in sera. METHODS: We assessed the sensitivity and specificity of the Tubex test among Tanzanian children hospitalized with febrile illness using blood culture as gold standard. Evaluation was done considering blood culture confirmed S. Typhi with non-typhi salmonella (NTS) and non - salmonella isolates as controls as well as with non-salmonella isolates only. RESULTS: Of 139 samples tested with Tubex, 33 were positive for S. Typhi in blood culture, 49 were culture-confirmed NTS infections, and 57 were other non-salmonella infections. Thirteen hemolyzed samples were excluded. Using all non - S. Typhi isolates as controls, we showed a sensitivity of 79% and a specificity of 89%. When the analysis was repeated excluding NTS from the pool of controls we showed a sensitivity of 79% and a specificity of 97%. There was no significant difference in the test performance using the two different control groups (p > 0.05). CONCLUSION: This first evaluation of the Tubex test in an African setting showed a similar performance to those seen in some Asian settings. Comparison with the earlier results of a Widal test using the same samples showed no significant difference (p > 0.05) for any of the performance indicators, irrespective of the applied control group.

Use of oral cholera vaccines in an outbreak in Vietnam: a case control study.

BACKGROUND: Killed oral cholera vaccines (OCVs) are available but not used routinely for cholera control except in Vietnam, which produces its own vaccine. In 2007-2008, unprecedented cholera outbreaks occurred in the capital, Hanoi, prompting immunization in two districts. In an outbreak investigation, we assessed the effectiveness of killed OCV use after a cholera outbreak began. METHODOLOGY/PRINCIPAL FINDINGS: From 16 to 28 January 2008, vaccination campaigns with the Vietnamese killed OCV were held in two districts of Hanoi. No cholera cases were detected from 5 February to 4 March 2008, after which cases were again identified. Beginning 8 April 2008, residents of four districts of Hanoi admitted to one of five hospitals for acute diarrhea with onset after 5 March 2008 were recruited for a matched, hospital-based, case-control outbreak investigation. Cases were matched by hospital, admission date, district, gender, and age to controls admitted for non-diarrheal conditions. Subjects from the two vaccinated districts were evaluated to determine vaccine effectiveness. 54 case-control pairs from the vaccinated districts were included in the analysis. There were 8 (15%) and 16 (30%) vaccine recipients among cases and controls, respectively. The vaccine was 76% protective against cholera in this setting (95% CI 5% to 94%, P = 0.042) after adjusting for intake of dog meat or raw vegetables and not drinking boiled or bottled water most of the time. CONCLUSIONS/SIGNIFICANCE: This is the first study to explore the effectiveness of the reactive use of killed OCVs during a cholera outbreak. Our findings suggest that killed OCVs may have a role in controlling cholera outbreaks.

The Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) initiative: a country-driven, multi-partner program to support evidence-based decision making.

Multiple health priorities, limited human resources and logistical capacities, as well as expensive vaccines with limited funds available increase the need for evidence-based decision making in immunization programs. The aim of the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative is to support countries in the establishment or strengthening of National Immunization Technical Advisory Groups (NITAGs) that provide recommendations on immunization policies and programs (e.g., vaccination schedules, improvements of routine immunization coverage, new vaccine introduction, etc.). SIVAC, a program funded by the Bill & Melinda Gates Foundation, is based on a country-driven, step-by-step process that ensures its support is tailored to country needs and emphasizes NITAG sustainability. SIVAC supports countries by reinforcing the capacities of the NITAG scientific and technical secretariat and by providing specific support activities established in consultation with the country and other international partners. Additionally, SIVAC and partners have built an electronic platform, the NITAG Resource Center, that provides information, tools, and briefings to NITAGs and the immunization community.

Searching for the elusive typhoid diagnostic.

Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.

Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data.

BACKGROUND: In Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined. METHODS: Reported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992). RESULTS: Two multi-year AVH outbreaks were identified: one during 1975-1976, and one during 1985-1987. During 1985-1987, AVH-associated MRs were 12.3-17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40-190 per 100,000) and among women aged 20-29 (15-21 per 100,000). During 1988-1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16-5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992. CONCLUSION: In the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985-1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.

Hepatitis A vaccine versus immune globulin for postexposure prophylaxis.

BACKGROUND: Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in preventing hepatitis A when given within 2 weeks after exposure to the virus. METHODS: We randomly assigned household and day-care contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days after exposure to patients with hepatitis A. Instances of laboratory-confirmed, symptomatic hepatitis A infection occurring between 15 and 56 days after exposure were then assessed during active follow-up of all susceptible contacts. RESULTS: Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among these contacts, 568 received hepatitis A vaccine and 522 received immune globulin. Most contacts were children (average age, 12 years), and most received prophylaxis during the second week after exposure (average interval after exposure, 10 days). The baseline characteristics of the contacts were similar in the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin (3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67). CONCLUSIONS: Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and immune globulin provided good protection after exposure. Although the study's prespecified criterion for noninferiority was met, the slightly higher rates of hepatitis A among vaccine recipients may indicate a true modest difference in efficacy and might be clinically meaningful in some settings. Vaccine has other advantages, including long-term protection, and it may be a reasonable alternative to immune globulin for postexposure prophylaxis in many situations. (ClinicalTrials.gov number, NCT00139139 [ClinicalTrials.gov].).

Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan.

Large outbreaks and sporadic cases of hepatitis E have been reported in Central Asia. We assessed the genetic relatedness of hepatitis E virus (HEV) strains from outbreak and sporadic cases in Turkmenistan. Specimens from outbreak and sporadic cases of acute hepatitis non-A, non-B were tested by reverse transcription (RT)-polymerase chain reaction (PCR) to identify the presence of HEV RNA; nucleotide sequences were analyzed. HEV RNA was detected from 23/156 (15%) outbreak cases and 2/23 (9%) sporadic cases. The HEV outbreak isolates represented 14 unique sequences with genetic distances varying between 0.3% and 8.6%, 12 of which were closely related, with distances between 0.3% and 5.6%. Two unique sequences from outbreak cases 32 and 42 were closely related (99.7%) and shared 91.8-93.4% of sequence with the other 12 strains. The two strains were closely related to the previously published isolates from Burma (99.7-100%) and India-Madras (95.7-96.1%). The two 1994 sporadic HEV strains were 97.4% distinct, wile revealing 91.4-94.1% homology to 1985 strains, and 94.4-94.7% to HEV from the neighboring China and Pakistan. Genetic diversity of HEV that caused the hepatitis E outbreak in Turkmenistan in 1985 suggests heterogeneity of viral sources. Sporadic hepatitis E that occurred in 1994 was caused by viral strains genetically distinct from those causing the outbreak in 1985, yet closely related to HEV from neighboring countries. The study suggests that circulation of a broad variety of strains of HEV may occur in Central Asia, regardless of international borders, presenting a significant public health threat to the population of the region.

Cost-analysis of different management policies for patients with mild hepatitis A virus infection in Kazakhstan.

OBJECTIVE: For patients with mild hepatitis A virus (HAV) infection, this study compared estimates of total costs associated with managing cases under a policy of mandatory hospitalization in the Republic of Kazakhstan and estimates of total costs associated with managing cases in outpatient settings. Costs were estimated both from the perspective of the Ministry of Health and from a broader societal perspective. METHODS: Data were collected by using a standardized structured questionnaire. For cases of mild HAV infection, medical records were obtained from 200 patients managed by hospitalization and from 251 patients managed in an outpatient setting. Personal interviews were also conducted to collect information on productivity losses and out-of-pocket expenses. RESULTS: Nationally, we estimated about 21,600 cases of mild HAV infection annually. The mean annual treatment costs in hospital for mild HAV infection was estimated at 3.39 million US dollars (2001 US dollars) (95% confidence interval [CI] = [3.26 million US dollars-3.52 million US dollars]). The total annual mild HAV infection cost to the society, including direct medical and nonmedical costs and productivity losses due to 721,440 lost work days, was estimated at 6.26 million US dollars (95% CI [6.05 million US dollars-6.47 million US dollars]). In sensitivity analyses, the total annual cost of mild HAV infection ranged from 4.37 million US dollars to 24.66 million US dollars. The survey results showed that a relatively minor change in the current policy of mandatory hospitalization could result in an estimated total annual savings of 4.62 million US dollars (2001 US dollars) in Kazakhstan. CONCLUSION: Adoption of an outpatient management policy for cases of mild HAV infection would generate substantial cost savings to the Ministry of Health and society.

Complete sequence of a Kyrgyzstan swine hepatitis E virus (HEV) isolated from a piglet thought to be experimentally infected with human HEV.

Hepatitis E virus (HEV) was identified by RT-PCR amplification with degenerate ORF2 primers in the stool of a piglet experimentally inoculated with a stool suspension from a patient with acute hepatitis during an outbreak of non-A, non-B hepatitis in Kyrgyzstan. Further characterization by sequencing of the complete genome and phylogenetic analysis showed that the piglet isolate was most closely related to HEV genotype 3. Because the original human stool specimen used to inoculate the piglet was no longer available, stool samples from three patients obtained during the same outbreak were sequenced and found to be HEV genotype 1. These findings suggest that the HEV isolated from the swine stool was probably an HEV enzootic in Kyrgyzstan and not the virus inoculated from the human stool.

Risk factors for human anthrax among contacts of anthrax-infected livestock in Kazakhstan.

A retrospective cohort analysis was conducted in Kazakhstan to define modifiable risk factors during seven outbreaks of human anthrax. Fifty-three cases and 255 non-ill persons with an epidemiologic link to an infected animal were enrolled. Cases were 58% male and had a median age of 35 years (range = 5-71). Nearly all cases had cutaneous disease (96%). Two patients (4%) were diagnosed with gastrointestinal disease. Although all cases had some contact with an infected animal other than consumption, in multivariable analysis the act of butchering an animal (relative risk [RR] = 3.6, 95% confidence interval [CI] = 1.5-9.6) and the presence of visible cuts on the hands were associated with anthrax (RR = 3.0, 95% CI = 0.9-9.6). Contact with infected livestock, in particular butchering, is associated with developing anthrax. The risk may be exacerbated by the presence of cuts on the hands at the time of contact with the animal or animal products.

Viral hepatitis serological markers among pregnant women in Caracas, Venezuela: implication for perinatal transmission of hepatitis B and C / Marcadores serológicos para hepatitis viral en embarazadas en Caracas, implicaciones para la transmisión perinatal de la hepatitis B y C

Viral hepatitis serological markers were analized in two groups of pregnant women residing in Caracas from:1) a maternity unit at the moment of delivery (106 sera, low income population), and 2) a private clinic during the third trimester of pregnancy (105 sera, medium-high economic class population). A higher percent positivity was observed in the maternity unit compared to the private clinic for hepatitis A virus (HAV) as measured by anti-HAV activity (96 por ciento vs 48 per cent; p<0.01 per cent), for hepatitis B virus (HBV) as measured by anti-HBc activity (13 per cent vs 2 per cent; p<0.01 per cent), but not for HBV carriage, as measured by HBsAg (3.8 per cent vs 0 per cent; p=0.06 per cent). These differences appear to correlate with the socio-economic level. All the HBsAg positive sera were HBsAg negative and negative for the presence of DNA by PCR, confirming the low rate of perinatal transmission observed in Venezuela. Two out of 106 sera (1.9 per cent) were positive for HCV antibodies in the maternity unit and 0/105 in the private clinic, although these differences were non significant (NS). Two out of 106 sera (1.9 per cent) were positive for HEV antibodies in the maternity unit and 1/80 (1.3 per cent) in the private clinic (NS). The anti-HEV seropositivity probably reflects a past infection. The importance of testing these viral markers during pregnancy is discussed