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BACKGROUND An increasingly crowded immunization schedule threatens the completion and compliance of hepatitis B vaccinations (HepB), the primary method of hepatitis B prevention. Combination vaccines have been proposed to alleviate this problem. METHODS Data from the 2011 National Immunization Survey Public-Use Data File were utilized (GSK study identifier: HO-11-770) to compare HepB completion and compliance rates between 3 groups of children: those who received HepB combination vaccine, those who received non-HepB combination vaccine and those who received HepB single-antigen vaccine only. Completion was defined as the accumulation of 3 HepB doses by 18 months. Compliance was defined as the receipt of vaccine doses within the Advisory Committee on Immunization Practices' recommended age ranges. RESULTS Of a sample of 4,040,116 children, 39.4% received a HepB combination vaccine, 43.0% received a non-HepB combination vaccine and 17.5% received a HepB single-antigen vaccine. Overall, 91.2% of children completed all 3 recommended doses, but only 61.8% completed them at age-appropriate times. Those receiving single-antigen only (odds ratio = 0.25, 95% confidence interval: 0.17-0.35) or non-HepB combination vaccines (odds ratio = 0.50, 95% confidence interval: 0.37-0.69) were substantially less likely to complete 3 doses of HepB than those who received the HepB combination vaccine. CONCLUSIONS Although completion rates were high, a large proportion of children did not receive HepB doses at age-appropriate times. Combination vaccine was associated with both higher completion and compliance outcomes compared with HepB single-antigen vaccine.

OBJECTIVE: To inform policy-makers about introduction of preventive interventions against typhoid, including vaccination. METHODS: A population-based prospective surveillance design was used. Study sites where typhoid was considered a problem by local authorities were established in China, India, Indonesia, Pakistan and Viet Nam. Standardized clinical, laboratory, and surveillance methods were used to investigate cases of fever of >or= 3 days' duration for a one-year period. A total of 441,435 persons were under surveillance, 159,856 of whom were aged 5-15 years. FINDINGS: A total of 21,874 episodes of fever were detected. Salmonella typhi was isolated from 475 (2%) blood cultures, 57% (273/475) of which were from 5-15 year-olds. The annual typhoid incidence (per 100,000 person years) among this age group varied from 24.2 and 29.3 in sites in Viet Nam and China, respectively, to 180.3 in the site in Indonesia; and to 412.9 and 493.5 in sites in Pakistan and India, respectively. Altogether, 23% (96/413) of isolates were multidrug resistant (chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole). CONCLUSION: The incidence of typhoid varied substantially between sites, being high in India and Pakistan, intermediate in Indonesia, and low in China and Viet Nam. These findings highlight the considerable, but geographically heterogeneous, burden of typhoid fever in endemic areas of Asia, and underscore the importance of evidence on disease burden in making policy decisions about interventions to control this disease.

Objective: To evaluate the safety and immunogenicity of revaccination with locally-produced Vi polysaccharide vaccine 3 years after the first dose in Chinese children aged 9 to 14 years. Methods: A randomized, placebo-controlled trial was conducted in Suzhou, Jiangsu, China. Six hundred and sixty-seven eligible children who had previously received a primary dose of Vi vaccine were randomly assigned to receive 1 dose of 30 μg Vi vaccine or placebo. In addition, 331 eligible children received 1 dose of Vi polysaccharide vaccine as a primary vaccination. Adverse events were followed for 28 days after vaccination. Serum samples were collected from a subgroup of participants on day 0 and day 28, and Vi antibodies were analyzed using a passive hemagglutination method. Results: Revaccination was found to be safe and immunogenic. No severe adverse events were observed. A significant increase in antibody titers after vaccination was observed among children who had and had not been previously vaccinated. Twenty-eight days after injection, the seropositive rate was 79% in both revaccination and primary injection groups; the geometric mean antibody titer was 1:40 in the primary injection group and 1:29 in the revaccination group (P = 0.24). Although the difference of attained geometric mean titers in follow-up sera was not significantly different in these 2 groups, the fold-rise of these titers from baseline was significantly higher in the primary injection group than in the revaccination group (7.7 versus 3.1, P < 0.001). Conclusion: We found that revaccination using the locally produced Vi polysaccharide vaccine among Chinese school-aged children was safe and increased antibody titers. Revaccination can be used to extend the duration of protection provided by Vi polysaccharide vaccine.

SUMMARYBlood culture-based diagnosis can only detect a fraction of the total burden ofSalmonella entericasubsp.entericaserovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex®and Typhidot-M®in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO⩾80 & TH>A), a positive Tubex®test (⩾4) and a positive Typhidot-M®test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.

Summary Objectives To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. Methods Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5°C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. Results During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. Conclusions This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

A locally produced Vi polysaccharide vaccine against typhoid fever was licensed in China following two placebo-controlled, efficacy trials conducted in the early 1990s in Baoying, Jiangsu Province, and Quan-zhou, Guangxi Province. The two trials each enrolled over 80,000 participants and followed participants for 12 and 19 months post-vaccination, respectively. To define the long-term efficacy of this vaccine, we retrospectively assessed the occurrence of typhoid fever, diagnosed with clinical and serological criteria, in the two study populations for 6 years following vaccination. During the second year following vaccination, vaccine efficacy was 100% (95% CI: 17%, 100%) in Baoying and 85% (95% CI: 49%, 96%) in Quan-zhou. There was suggestive protection (51%; PE: -95%, 88%) during the third year in Baoying, nearly identical to the level observed in the third year of an earlier trial in South Africa. These results confirm that this vaccine protects for at least 2 years, and are consistent with the assertion that the vaccine protects for at least 3 years.

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings.

Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83→Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB , parC , or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.

Two currently licensed typhoid vaccines have been evaluated in Asia, yet few Asian countries have considered including typhoid vaccines in their vaccination programs. The Diseases of the Most Impoverished (DOMI) Program was initiated to provide evidence to decide on the introduction of typhoid vaccines in Asian countries.The centerpiece of the program is a multidisciplinary demonstration project with Vi vaccine in 5 Asian countries. The project includes epidemiologic, economic, sociobehavioral, and policy studies.Policy makers want evidence on which to base their vaccine-related decisions. The DOMI Program has provided updated information on the typhoid fever burden at several Asian sites. Cost-of-illness studies found high costs to governments and individuals. Sociobehavioral studies indicated a positive attitude toward typhoid vaccines. The results of the demonstration projects indicate that mass-immunization campaigns are feasible and acceptable.The DOMI Program has begun to provide momentum for the evidence-based, rational introduction of typhoid vaccines into the public health programs of several Asian countries.

INTRODUCTION: In research projects such as vaccine trials, accurate and complete surveillance of all outcomes of interest is critical. In less developed countries where the private sector is the major health-care provider, the private sector must be included in surveillance systems in order to capture all disease of interest. This, however, poses enormous challenges in practice. The process and outcome of recruiting private practice clinics for surveillance in a vaccine trial are described. METHODS: The project started in January 2002 in two urban squatter settlements of Karachi, Pakistan. At the suggestion of private practitioners, a phlebotomy team was formed to provide support for disease surveillance. Children who had a reported history of fever for more than three days were enrolled for a diagnosis. RESULTS: Between May 2003 and April 2004, 5540 children younger than 16 years with fever for three days or more were enrolled in the study. Of the children, 1312 (24%) were seen first by private practitioners; the remainder presented directly to study centres. In total, 5329 blood samples were obtained for microbiology. The annual incidence of Salmonella typhi diagnosed by blood culture was 407 (95% confidence interval (95% CI), 368-448) per 100 000/year and for Salmonella paratyphi A was 198 (95% CI, 171-227) per 100 000/year. Without the contribution of private practitioners, the rates would have been 240 per 100 000/year (95% CI, 211-271) for S. typhi and 114 (95% CI, 94-136) per 100 000/year for S. paratyphi A. CONCLUSION: The private sector plays a major health-care role in Pakistan. Our experience from a surveillance and burden estimation study in Pakistan indicates that this objective is possible to achieve but requires considerable effort and confidence building. Nonetheless, it is essential to include private health care providers when attempting to accurately estimate the burden of disease in such settings.

Objective To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. Methods A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. Results The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. Conclusion This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

The practicalities when applying the ICH GCPs (International Conference on Harmonization 1996 Good Clinical Practices [EU, MHLW, FDA. International Conference on Harmonization Guideline for Good Clinical Practice; 1997] in less developed countries (ldcs) are seldom discussed and we found no guidelines as how to “adapt” them. Below we illustrate how ICH GCP principles can be implemented in different settings. We have recently conducted in Asia (Hechi, China; Karachi, Pakistan; Hue, Vietnam; North Jakarta, Indonesia and Kolkata, India) large-scale cluster-randomized effectiveness evaluations of the Vi polysaccharide typhoid fever vaccine (Vi PS project) among approximately 200,000 individuals 1 [Acosta CJ, Galindo CM, Ali M, Abu-Elyazeed R, Ochiai RL Danovaro-Holliday MC et al. A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design. TMIH 2005;10(12):1219–1228] . There is no doubt on the importance of ICH GCP in its contribution to ethical and scientifically sound clinical research. However, when the ICH GCP is implemented in ldcs some considerations must be made in order to adequately tailor them. Vaccine trials in ldcs are a frequent setting for such challenges because of the increased global interest conducting health research in such countries. The ICH GCP principles are discussed below within the framework of this recent typhoid fever vaccine study experience.

Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.

Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases.

Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities.

Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility.832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys.The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]).Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.The impact of iron supplementation and malaria chemoprophylaxis was investigated in a double-blind, placebo-controlled study involving 832 infants born in a malaria-hyperendemic area of Tanzania in 1995. Infants were randomly assigned to receive daily oral iron (2 mg/kg) and weekly Deltaprim (3-125 mg pyrimethamine plus 25 mg dapsone), daily iron plus weekly placebo, or daily and weekly placebo. Daily supplementation was provided from 8 to 24 weeks of age, while weekly chemoprophylaxis was given from 8 to 48 weeks. The 2 groups that received iron supplementation had a lower frequency of severe anemia (packed cell volume under 25%) than those who received placebo (0.62 versus 0.87 cases per person-year; protective efficacy, 28.8%), but iron supplementation did not have a significant effect on malaria incidence (0.87 versus 1.00 cases per person-year; protective efficacy, 12.8%). Infants who received malaria prophylaxis had lower frequencies of both severe anemia (0.45 versus 1.04 episodes per person-year; protective efficacy, 57.3%) and malaria (0.53 versus 1.43 episodes per person-year; protective efficacy, 60.5%) than those who received placebo. However, after the end of the intervention period, children who had received malaria prophylaxis had higher rates of severe anemia and malaria than those in the non-chemoprophylaxis groups (relative risks, 2.2 and 1.8, respectively). These findings indicate that malaria chemoprophylaxis during the first year of life can impair the development of natural immunity, while iron supplementation effectively prevents severe anemia without increasing susceptibility to malaria.

To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.

Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.