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Cholera causes substantial morbidity and mortality in the world's poorest populations. For nearly a decade, an inactivated oral cholera vaccine (OCV) stockpile has been available to control and prevent outbreaks. In 2017, WHO launched a bold global initiative to reduce mortality from cholera by 90% by 2030, a cornerstone of which is deployment of OCVs from the global stockpile. The current production of OCVs for the stockpile falls well short of the doses needed to accomplish this goal. Besides efforts to enlist additional manufacturers of the current OCVs in the stockpile, inclusion of new-generation inactivated OCVs already in clinical development might offer advantages of enlarged production, improved performance, simplified logistics, and reduced costs. However, logistical, scientific, and ethical barriers make conventional, randomised, phase 3 clinical efficacy trials towards licensure of such new-generation OCVs problematic. The serum vibriocidal antibody response, the traditional immunological surrogate of protection against cholera, is imperfect for use as a standalone outcome. In this Personal View, we describe the need for new thinking on approaches for licensure and recommendations for new-generation inactivated OCVs, and suggest a pathway based on a sequential combination of immunogenicity and effectiveness observational studies. [ABSTRACT FROM AUTHOR]

Cholera is an ancient disease that remains a public health problem in many impoverished locations around the world. Seven pandemics of cholera have been recorded since the first pandemic in 1817, the last of which is on going. Overcrowding, poverty, insufficient water and sanitation facilities increase the risk for cholera outbreaks. The epidemiology of cholera in the areas in Asia, Africa and the Americas where the disease occurs continues to evolve. [ABSTRACT FROM AUTHOR]

Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. The supply of licensed, WHO-prequalified cholera vaccines is not sufficient to meet endemic and epidemic needs worldwide and so prioritisation is needed. We have developed a scenario approach to systematically classify situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world and provides evidence that we hope will spur the development of detailed guidelines on how and where oral cholera vaccines could, and should, be most rationally deployed. [ABSTRACT FROM AUTHOR]

Summary: Information about community-acquired bacteraemia in developing countries in south and southeast Asia is scarce. We aimed to establish the case fraction of bacteraemia in febrile patients admitted to hospital. We searched four databases and identified studies of south and southeast Asia published between 1990 and 2010 that prospectively assessed patients admitted to hospital and from whom a blood culture was taken. We reviewed 17 eligible studies describing 40 644 patients. Pathogenic organisms were isolated from 3506 patients (9%; range 1–51%); 1784 (12%) of 14 386 adults and 1722 (7%) of 26 258 children. Salmonella enterica serotype Typhi was the most common bacterial pathogen, accounting for 532 of 1798 (30%) isolates in adults and 432 of 1723 (25%) in children. Other commonly isolated organisms in adults were Staphylococcus aureus, Escherichia coli, and other Gram-negative organisms, and in children were Streptococcus pneumoniae and Haemophilus influenzae. A substantial case fraction of bacteraemia occurs in patients admitted to hospital with fever in this region. Management could be improved if diagnostic microbiology facilities were more widely available. The prevailing organisms causing bacteraemia and their susceptibility patterns could inform empirical treatment regimens and prevention strategies. [ABSTRACT FROM AUTHOR]

Abstract: Vibrio cholerae O1 strains that are hybrids between the classical and El Tor biotypes were isolated during two consecutive years (2004–2005) from diarrheal patients in Mozambique. Similar variants isolated in Bangladesh and recently isolated El Tor strains were analyzed for genetic diversity. Pulsed-field gel electrophoresis (PFGE) analysis using the restriction enzyme NotI, resulted in 18–21 bands showed five closely related PFGE patterns that were distributed similarly in both years (2004–2005) among the 80 strains tested in Mozambique. Overall based on the PFGE patterns the hybrids indicated an El Tor lineage. The restriction patterns of whole-chromosomal DNA grouped the hybrid strains from Mozambique into a separate cluster from Bangladeshi clinical and environmental hybrid strains. A high molecular weight band of 398kb that contain rstR allele of the classical type was detected from all hybrid strains, which was absent in all conventional classical and El Tor strains. This band could be designated as a marker for the hybrid strains. This study suggests that hybrid strains from Mozambique are closely related to each other, different from Bangladeshi hybrid strains that are diverse in nature and all hybrid strains differed markedly from conventional classical and El Tor strains. [Copyright &y& Elsevier]

Abstract: We assessed the long-term protection afforded by a killed whole-cell oral cholera vaccine produced in Vietnam. A mass immunization of children and adults with the killed whole-cell oral cholera vaccine was undertaken in half of the communes of Hue, Vietnam, in 1998; the remaining communes were immunized in 2000. No cholera was observed in Hue until 2003, when an outbreak of El Tor cholera made it possible to conduct a case–control study. The overall vaccine effectiveness 3–5 years after vaccination was 50% (9–63%). This low-cost, easily administered vaccine should be considered as a tool for the control of cholera. [Copyright &y& Elsevier]

A survey of policymakers and other influential professionals in four southeast Asian countries (Cambodia, Indonesia, Philippines and Vietnam) was conducted to determine policymakers’ views on the public health importance of dengue fever and dengue haemorrhagic fever (DHF), the need for a vaccine and the determinants influencing its potential introduction. The survey, which involved face-to-face interviews with policymakers, health programme managers, researchers, opinion leaders and other key informants, revealed an almost uniformly high level of concern about dengue fever/DHF and a high perceived need for a dengue vaccine. Several characteristics of the disease contribute to this high sense of priority, including its geographic spread, occurrence in outbreaks, the recurrent risk of infection each dengue season, its severity and the difficulty in diagnosis and management, its urban predominance, its burden on hospitals, and its economic toll on governments and families. Research felt to be key to future decision-making regarding dengue vaccine introduction include: disease surveillance studies, in-country vaccine trials or pilot projects, and studies on the economic burden of dengue and the cost-effectiveness of dengue vaccines. The results suggest favourable conditions for public and private sector markets for dengue vaccines and the need for creative financing strategies to ensure their accessibility to poor children in dengue-endemic countries. [Copyright &y& Elsevier]

COVID-19 spreads via aerosols, droplets, fomites and faeces. The built environment that facilitates crowding increases exposure and hence transmission of COVID-19 as evidenced by outbreaks in both cool-dry and hot-humid climates, such as in the US prison system and dormitories in Singapore, respectively. This paper explores how the built environment influences crowding and COVID-19 transmission, focusing on informal urban settlements (slums). We propose policy and practice changes that could reduce COVID-19 transmission. There are several issues on how COVID-19 affects informal urban settlements. Slum populations tend to be younger than the overall population. Lower numbers of older people lessen the morbidity and mortality of the pandemic in slum areas. Second, many slum populations are highly mobile. By returning to their ancestral villages residents can avoid the risks of overcrowding and reduce the population density in a given area but may spread COVID-19 to other areas. Third, detection and registration of COVID-19 cases depends on patients presenting to health care providers. If the risk of visiting a health care centre outweighs the potential benefits patients may prefer not to seek treatment. The control and prevention of COVID-19 in informal urban settlements starts with organizing community infrastructure for diagnosis and treatment and assuring that basic needs (food, water, sanitation, health care and public transport) are met during quarantine. Next, community members at highest risk need to be identified and protected. Low-income, informal settlements need to be recognized as a reservoir and source for persistent transmission. Solutions to overcrowding must be developed for this and future pandemics. In view of the constant risk that slums present to the entire population decisive steps need to be taken to rehabilitate and improve informal settlements, while avoiding stigmatization. [ABSTRACT FROM AUTHOR]

A three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections. In this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9–14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline. A single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20–88; p=0·017) and the entire follow-up period (67%, 19–87; p=0·016). The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines. The Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Abstract: In the summer of 2005, we interviewed 996 randomly selected respondents in Beira, Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members. Respondents were told that two doses of the vaccine would be required 2 weeks apart, and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination, and some protection during the second and third year after a person is vaccinated. This research was carried out in order to learn more about private demand for vaccines in a cholera-endemic area. We asked two types of valuation questions: (1) a discrete-price offer for a vaccine that could be purchased for household members and (2) a payment card designed to assess uncertainty in the respondent''s demand for a vaccine for self-protection. We estimate average household willingness to pay (WTP) for cholera vaccines in Beira to be 2005 US$ 8.45. This estimate of household WTP represents the perceived private economic benefits to a household – six persons on average – of giving all members free cholera vaccines. [Copyright &y& Elsevier]

Dengue fever is an important public health problem in the Philippines. In April 2016, the Department of Health launched a three-dose school based dengue vaccination program of nine- to fourteen-year-old children in three regions with the highest number of dengue cases using CYD-TDV (Dengvaxia, Sanofi Pasteur). In July 2017, a community-based dengue vaccination program was implemented in Cebu province. The program was discontinued in December 2017 amidst public controversy, after the first dose had been administered. We assessed the effectiveness of a single dose of CYD-TDV against hospitalized virologically confirmed dengue (VCD). We conducted a case-control study in Cebu province following the dengue mass vaccination. Children who were nine to fourteen years of age during the mass vaccination and subsequently admitted to any of four participating public hospitals with suspected dengue were enrolled in the study as cases. Blood for RT-PCR and clinical and socio-demographic information were obtained. To estimate the level of vaccine protection, vaccination status was compared between children with hospitalized virologically confirmed dengue and controls of the same six-year age-group as the cases, matched on sex, neighborhood and time of occurrence of cases. We enrolled 490 cases and 980 controls. Receipt of one dose of CYD-TDV was associated with 26% (95 % CI, −2 to 47%; p = 0 0675) overall protection against hospitalized virologically confirmed dengue and 51% (95 % CI, 23 to 68; p = 0 0016) protection against dengue with warning signs. A single dose of CYD-TDV given to nine to fourteen-year-old children through a community-based mass vaccination program conferred protection against dengue with warning signs and severe dengue but we were unable to conclude on protection against milder illness. [ABSTRACT FROM AUTHOR]

Vaccination with the first licensed dengue vaccine is recommended only for those who have had previous infection with dengue virus (DENV). A point-of-care test with the desired sensitivity of 95% and specificity of 98% could facilitate pre-vaccination screening. We evaluated a newly developed, automated dengue immunoglobulin fluorescence immunoassay for determining dengue serostatus. We used serum samples collected just prior to a mass dengue vaccination in Cebu, Philippines. Healthy children residing in Bogo and Balamban who would be 9–14 years old at the time of the mass dengue vaccination were eligible to participate. We evaluated the ichroma™ II dengue fluorescence immunoassay (Boditech Med Incorporated, Gang-won-do, Republic of Korea) using a neutralization test (NT) as the reference assay. We enrolled 2996 children (mean age 10.39 years, 51.7% female) in the cohort and included a subsample of 1000 (mean age 10.56 years, 54.4% female) in this study. Of the 1000 children, 86/1000 (8.6%) tested seronegative and 914/1000 (91.4%) seropositive for DENV antibodies by neutralization testing. Compared with the NT, the dengue IgG fluorescence immunoassay had an overall specificity of 90.7% (95%CI: 82.5–95.9%) and a sensitivity of 91.8% (95%CI: 89.8–93.5%) for determining dengue seropositivity. The sensitivity declined to 51.2% (42.3–61.0%) for the detection of the subset with a monotypic dengue profile. The insufficient specificity and sensitivity (particularly in the detection of a previous monotypic dengue infection) would render the test, in its current state, inadequate for pre-vaccination screening. Considering its user-friendly interphase and possibility of point-of-care use, the test could be further developed and validated to improve its performance characteristics. [ABSTRACT FROM AUTHOR]

Background The test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses. Methods Randomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status ( Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE = (1 − OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1 − hazard ratio)×100%). Results OCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37–62%; Kolkata: 67%, 95% CI:57–75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43–60% and Kolkata: 66%, 95% CI:55–74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84–98%) compared with 82% (95% CI:58–93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates. Conclusion Our findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs. [ABSTRACT FROM AUTHOR]

Background Case–control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. Methods We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case–control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding “virtual” cluster. Specific selection strategies were used to evaluate the vaccine protective effects. Results 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47–91%) protection in a cohort analysis and 84% (95% CI: 60–94%) in case–control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10–74%) in cohort and 76% (95% CI: 47–89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case–control analyses. Conclusion The findings show that case–control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. [ABSTRACT FROM AUTHOR]

Summary: Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. Findings: 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52–74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. [ABSTRACT FROM AUTHOR]

Summary: Background: Zanzibar, in east Africa, has been severely and repeatedly affected by cholera since 1978. We assessed the effectiveness of oral cholera vaccination in high-risk populations in the archipelago to estimate the indirect (herd) protection conferred by the vaccine and direct vaccine effectiveness. Methods: We offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites. To estimate vaccine direct protection, we compared the incidence of cholera between recipients and non-recipients using generalised estimating equations with the log link function while controlling for potential confounding variables. To estimate indirect effects, we used a geographic information systems approach and assessed the association between neighbourhood-level vaccine coverage and the risk for cholera in the non-vaccinated residents of that neighbourhood, after controlling for potential confounding variables. This study is registered with ClinicalTrials.gov, number NCT00709410. Findings: Of 48 178 individuals eligible to receive the vaccine, 23 921 (50%) received two doses. Between February, 2009, and May, 2010, there was an outbreak of cholera, enabling us to assess vaccine effectiveness. The vaccine conferred 79% (95% CI 47–92) direct protection against cholera in participants who received two doses. Indirect (herd) protection was shown by a decrease in the risk for cholera of non-vaccinated residents within a household''s neighbourhood as the vaccine coverage in that neighbourhood increased. Interpretation: Our findings suggest that the oral cholera vaccine offers both direct and indirect (herd) protection in a sub-Saharan African setting. Mass oral cholera immunisation campaigns have the potential to provide not only protection for vaccinated individuals but also for the unvaccinated members of the community and should be strongly considered for wider use. Because this is an internationally-licensed vaccine, we could not undertake a randomised placebo-controlled trial, but the absence of vaccine effectiveness against non-cholera diarrhoea indicates that the noted protection against cholera could not be explained by bias. Funding: Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, and the South Korean Government. [Copyright &y& Elsevier]

Summary: The “old” familiar diseases of cholera and typhoid remain a serious health threat in many developing countries. Health policy analysts often argue that vaccination against cholera and typhoid should be provided free because poor people cannot afford to pay for such vaccines and because vaccination confers positive economic externalities on unvaccinated individuals. In 2004, we conducted a contingent valuation (CV) survey of 835 randomly selected adults from two neighborhoods in Kolkata, India to provide information on private demand for cholera and typhoid vaccines for themselves and for household members to support more nuanced financial and economics analyses of such vaccination programs. The median private economic benefits of providing a typhoid vaccine to a household with five members is about US$23 in a middle-income neighborhood (US$27 for a cholera vaccine) and US$14 in a low-income slum (US$15 for a cholera vaccine). Our research raises an intriguing possibility. If user charges were set at a level to recover the costs of a vaccination program, there could be sufficient demand for the vaccine so that coverage of the vaccinated population might ensure that all the remaining unvaccinated individuals would be protected as well through indirect herd protection. [Copyright &y& Elsevier]

Objectives: This study aims to measure the private demand for oral cholera vaccines in Hue, Vietnam, an area of relatively low endemicity of cholera, using the contingent valuation method. Methods: Interviews were conducted with either the head of household or spouse in 800 randomly selected households with children less than 18 years old. Respondents were asked whether they would purchase an oral cholera vaccine with different levels of effectiveness and durations of effectiveness (both for themselves and for other household members) at a specified price. Results: The median respondent willingness to pay for 50% effective/3-year vaccine was estimated to be approximately $5, although 17% of the study sample would not pay for a cholera vaccine. The median economic benefit to a household of vaccinating all household members against cholera, as measured by its stated willingness to pay, was estimated to be $40 for a vaccine with these attributes. Conclusions: The perceived private economic benefits of a cholera vaccine were high, but not evenly distributed across the population. A minority of the people in Hue place no value on receiving a cholera vaccine. [ABSTRACT FROM AUTHOR]

Abstract: Vietnam currently produces an orally administered, bivalent (O1 and O139) killed whole-cell vaccine and is the only country in the world with endemic cholera to use an oral cholera vaccine in public health practice. In order to allow international use, the vaccine had to be reformulated to meet World Health Organization (WHO) requirements. We performed a randomized, placebo controlled, safety and immunogenicity studies of this reformulated vaccine among Vietnamese adults. One hundred and forty-four subjects received the two-dose regimen and 143 had two blood samples obtained for analysis. We found that this reformulated oral killed whole-cell cholera vaccine was safe, well tolerated and highly immunogenic. [Copyright &y& Elsevier]

Abstract: Although typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi, rapid and simple diagnostic serologic tests would be useful in developing countries. We examined the performance of Widal test in a community field site and compared it with Typhidot and Tubex tests for diagnosis of typhoid fever. Blood samples were collected from 6697 patients with fever for ≥3 days for microscopy, culture, and serologic testing and from randomly selected 172 consenting healthy individuals to assess the baseline Widal anti-Typhi O lipopolysaccharide antibody (anti-TO) and anti-Typhi H flagellar antibody (anti-TH) titers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 3 serologic tests were calculated using culture-confirmed typhoid fever cases as “true positives” and paratyphoid fever and malaria cases as “true negatives”. Comparing cutoff values for the Widal test, an anti-TO titer of 1/80 was optimal with 58% sensitivity, 85% specificity, 69% PPV, and 77% NPV. Sensitivity was increased to 67% when the Widal test was done on the 5th day of illness and thereafter. The sensitivity, specificity, PPV, and NPV of Typhidot and Tubex were not better than Widal test. There is a need for more efficient rapid diagnostic test for typhoid fever especially during the acute stage of the disease. Until then, culture remains the method of choice. [Copyright &y& Elsevier]

Abstract: We conducted a study to assess the feasibility and the potential vaccine coverage of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban endemic neighbourhood of Beira, Mozambique. The campaign was conducted from December 2003 to January 2004. Overall 98,152 doses were administered, and vaccine coverage of the target population was 58.6% and 53.6% for the first and second rounds, respectively. The direct cost of the campaign, which excludes the price of the vaccine, amounted to slightly over $90,000, resulting in the cost per fully vaccinated person of $2.09, which is relatively high. However, in endemic settings where outbreaks are likely to occur, integrating cholera vaccination into the routine activities of the public health system could reduce such costs. [Copyright &y& Elsevier]

Introduction: Targeted cholera immunization of high-risk populations in Vietnam is conducted based on routine surveillance data. Following mass immunization of schoolchildren in Ca Mau City using an oral bivalent killed cholera vaccine, adverse reactions were noted.Methods: Salient data were collected in a systematic fashion including the review of medical records; interview of the school principal, teachers, students, parents and doctors; and review of the storage and handling of the vaccine.Findings: On 18 December 2001, 234 children at a primary school in Ca Mau City received the cholera vaccine. Within 1 h of immunization, three children in one of the classrooms complained of trembling, nausea and headache and were brought to the library and soon other children followed. Out of 234, 97 (42%) pupils were affected and brought to the Municipal Health Center or Ca Mau Provincial Hospital. Those who were affected were younger (mean age=9.6 years; 95% CI=9.4–9.7) compared to those who were not affected (mean age=10 years; 95% CI=9.7–10.3; t-test=−2.4; P-value=0.02). The proportion of affected females among those who had received the vaccine (49/114 or 43%) was similar to the proportion in males (48/120 or 40%; RR=1.07; 95% CI=0.79–1.46). The most frequent presenting complaint was cold extremities (60%) followed by headache (27%). All affected children recovered and were discharged in a few hours. None reported any sequelae or relapse. Once the situation was recognized, the cholera immunization campaign was continued. Laboratory tests of vaccine samples from the same batch detected no abnormality or contaminating agent.Discussion: The findings suggest that the children at primary school number 1 suffered from a mass psychogenic illness. This incident was unusual in that a similar number of boys and girls were affected, in contrast to the frequently reported preponderance of female cases. Furthermore the underlying cause was very quickly diagnosed, medical interventions were kept to a minimum, and no relapse was observed. Future vaccination campaigns have to assure that the families are informed in advance. [Copyright &y& Elsevier]

Summary: Background: Pneumococcal colonization of the nasopharynx is especially common in young children and is a pre-requisite for pneumococcal disease. Those with immunosuppression, such as HIV, are at higher risk of colonization and disease, especially at older ages. Currently, vaccination schedules are only offered to children under 6 months of age, despite the large impact of pneumococcal disease in older unvaccinated children with HIV. We conducted a study to assess the prevalence of, and risk factors for, pneumococcal carriage in HIV-positive children aged <15 years. Methods: We collected a single nasopharyngeal swab from 142 HIV-infected children aged 1–14 years over a 2-month period. To detect carriage of pneumococcus, these samples were cultured and serotyped; PCR was performed on negative samples. We also collected epidemiological data via survey and medical records. Results: The overall carriage rate was 81% and was at least 76% in those aged 5–14 years. The 7-, 10-, and 13-valent pneumococcal vaccines would cover 37%, 37%, and 49% of children with carriage, respectively. In the multivariate analysis, we identified increase in weight since last visit (p =0.028) and the existence of care-givers who had respiratory symptoms in the past week (p =0.022) as risk factors for carriage. Weight gain was also significantly associated with antiretroviral use (p =0.002). Conclusions: These data illuminate the little known area of pneumococcal carriage in older HIV-infected children as well as finding novel risk factors for pneumococcal carriage, namely the association with household members who have respiratory symptoms and with an increase in the child''s weight prior to swabbing. Weight gain may be due to an increase in health enabling more mobility and increasing the risk of acquiring carriage. The carriage rate observed (81%) is one of the highest recorded. Further research should address whether vaccination can prevent the acquisition of carriage and so protect against disease. [Copyright &y& Elsevier]