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.     

Improving community coverage of oral cholera mass vaccination campaigns: lessons learned in zanzibar

Background

Recent research in two cholera-endemic communities of Zanzibar has shown that a majority (∼94%) of the adult population was willing to receive free oral cholera vaccines (OCVs). Since OCV uptake in the 2009 campaign reached only ∼50% in these communities, an evaluation of social and cultural factors and of barriers was conducted to understand this difference for future cholera control planning.

Methodology/Principal Findings

A random sample of 367 adult peri-urban and rural community residents (46.6% immunized vs. 53.4% unimmunized) was studied with a semi-structured interview that inquired about social and cultural features of cholera depicted in a vignette and barriers to OCV uptake. Symptoms (rectal pain, loose skin only in rural community) and perceived causes (uncovered food, contact with contaminated water) specific for severe diarrhea were associated with uptake. Purchasing drugs from pharmacies to stop diarrhea and vomiting was negatively associated with uptake. Increasing household size, age and previous enteric illness episode were positively related to uptake, the latter only at the rural site. The most prominent barrier to uptake was competing obligations or priorities (reported by 74.5%, identified as most important barrier by 49.5%). Next most prominent barriers were lacking information about the campaign (29.6%, 12.2%), sickness (14.3%, 13.3%) and fear of possible vaccine side effects (15.3%, 5.6%). The majority of unvaccinated respondents requested repetition of the vaccination with free OCVs.

Conclusions/Significance

Factors associated with uptake indicated a positive impact of the vaccination campaign and of sensitization activities on vaccine acceptance behavior. Unlike communities opposed to cholera control or settings where public confidence in vaccines is lacking, identified barriers to uptake indicated a good campaign implementation and trust in the health system. Despite prospects and demand for repeating the vaccination, local decision-makers should reconsider how careful logistical arrangements may improve community coverage and thus effectiveness of vaccination campaigns.     

Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial

Background

Killed oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.

Methods/Principal Findings

We conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups.

Conclusions/Significance

The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine''s duration of protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00289224","term_id":"NCT00289224"}}NCT00289224.     

Sudden unexpected deaths and vaccinations during the first two years of life in Italy: a case series study

Background

The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy.

Methodology/Principal Findings

The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined.

Conclusions

The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age.     

Cross-sectional analysis of late HAART initiation in Latin America and the Caribbean: late testers and late presenters

Background

Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region.

Methodology

Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4⁺ count ≤200cells/mm³ prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed.

Principal Findings

Among subjects starting HAART (n = 9817) who had baseline CD4⁺ available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52–59]), Chile (80%[95%CI:77–82]), Haiti (76%[95%CI:74–77]), Honduras (91%[95%CI:87–94]), Mexico (79%[95%CI:75–83]), Peru (86%[95%CI:84–88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02–1.45; OR 1.20, 95%CI:1.02–1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94–1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87–0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP.

Conclusion

LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation are needed to maximize benefits from HAART in the region.     

The prevalence and risk factors for pneumococcal colonization of the nasopharynx among children in Kilifi District, Kenya

Background

Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine-serotype pneumococci but increase in the carriage of non-vaccine serotypes. We studied the epidemiology of carriage among children 3–59 months old before vaccine introduction in Kilifi, Kenya.

Methods

In a rolling cross-sectional study from October 2006 to December 2008 we approached 3570 healthy children selected at random from the population register of the Kilifi Health and Demographic Surveillance System and 134 HIV-infected children registered at a specialist clinic. A single nasopharyngeal swab was transported in STGG and cultured on gentamicin blood agar. A single colony of pneumococcus was serotyped by Quellung reaction.

Results

Families of 2840 children in the population-based sample and 99 in the HIV-infected sample consented to participate; carriage prevalence was 65.8% (95% CI, 64.0–67.5%) and 76% (95% CI, 66–84%) in the two samples, respectively. Carriage prevalence declined progressively with age from 79% at 6–11 months to 51% at 54–59 months (p<0.0005). Carriage was positively associated with coryza (Odds ratio 2.63, 95%CI 2.12–3.25) and cough (1.55, 95%CI 1.26–1.91) and negatively associated with recent antibiotic use (0.53 95%CI 0.34–0.81). 53 different serotypes were identified and 42% of isolates were of serotypes contained in the 10-valent PCV. Common serotypes declined in prevalence with age while less common serotypes did not.

Conclusion

Carriage prevalence in children was high, serotypes were diverse, and the majority of strains were of serotypes not represented in the 10-valent PCV. Vaccine introduction in Kenya will provide a natural test of virulence for the many circulating non-vaccine serotypes.     

Increased population prevalence of low pertussis toxin antibody levels in young children preceding a record pertussis epidemic in Australia

Background

Cross-sectional serosurveys using IgG antibody to pertussis toxin (IgG-PT) are increasingly being used to estimate trends in recent infection independent of reporting biases.

Methods/Principal Findings

We compared the age-specific seroprevalence of various levels of IgG-PT in cross-sectional surveys using systematic collections of residual sera from Australian diagnostic laboratories in 1997/8, 2002 and 2007 with reference to both changes in the pertussis vaccine schedule and the epidemic cycle, as measured by disease notifications. A progressive decline in high-level (≥62.5 EU/ml) IgG-PT prevalence from 19% (95% CI 16–22%) in 1997/98 to 12% (95% CI 11–14%) in 2002 and 5% (95% CI 4–6%) in 2007 was consistent with patterns of pertussis notifications in the year prior to each collection. Concomitantly, the overall prevalence of undetectable (<5 EU/ml) levels increased from 17% (95% CI 14–20%) in 1997/98 to 38% (95% CI 36–40%) in 2007 but among children aged 1–4 years, from 25% (95% CI 17–34%) in 1997/98 to 62% (95% CI 56–68%) in 2007. This change followed withdrawal of the 18-month booster dose in 2003 and preceded record pertussis notifications from 2008 onwards.

Conclusions/Significance

Population seroprevalence of high levels of IgG-PT is accepted as a reliable indicator of pertussis disease activity over time within and between countries with varying diagnostic practices, especially in unimmunised age groups. Our novel findings suggest that increased prevalence of undetectable IgG-PT is an indicator of waning immunity useful for population level monitoring following introduction of acellular vaccines and/or schedule changes.     

Dog bites in humans and estimating human rabies mortality in rabies endemic areas of Bhutan

Background

Dog bites in humans are a public health problem worldwide. The issues of increasing stray dog populations, rabies outbreaks, and the risk of dogs biting humans have been frequently reported by the media in Bhutan. This study aimed to estimate the bite incidence and identify the risk factors for dog bites in humans, and to estimate human deaths from rabies in rabies endemic south Bhutan.

Methods

A hospital-based questionnaire survey was conducted during 2009–2010 among dog bites victims who visited three hospitals in Bhutan for anti-rabies vaccine injection. Decision tree modeling was used to estimate human deaths from rabies following dog bite injuries in two rabies endemic areas of south Bhutan.

Results

Three hundred and twenty four dog bite victims were interviewed. The annual incidence of dog bites differed between the hospital catchment areas: 869.8 (95% CI: 722.8–1022.5), 293.8 (240–358.2) and 284.8 (251.2–323) per 100,000 people in Gelephu, Phuentsholing and Thimphu, respectively. Males (62%) were more at risk than females (P<0.001). Children aged 5–9 years were bitten more than other age groups. The majority of victims (71%) were bitten by stray dogs. No direct fatal injury was reported. In two hospital areas (Gelephu and Phuentsholing) in south Bhutan the annual incidence of death from rabies was 3.14 (95% CI: 1.57–6.29) per 100,000 population. The decision tree model predicted an equivalent annual incidence of 4.67 (95% CI: 2.53–7.53) deaths/100,000 population at risk. In the absence of post exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69–25.14) deaths/year in these two areas.

Conclusions

Increased educational awareness of people about the risk of dog bites and rabies is necessary, particularly for children in rabies endemic areas of Bhutan.     

Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: a systematic review

Background

Recent reports of high HIV infection rates among men who have sex with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income countries. To investigate the global epidemic of HIV among MSM and the relationship of MSM outbreaks to general populations, we conducted a comprehensive review of HIV studies among MSM in low- and middle-income countries and performed a meta-analysis of reported MSM and reproductive-age adult HIV prevalence data.

Methods and Findings

A comprehensive review of the literature was conducted using systematic methodology. Data regarding HIV prevalence and total sample size was sequestered from each of the studies that met inclusion criteria and aggregate values for each country were calculated. Pooled odds ratio (OR) estimates were stratified by factors including HIV prevalence of the country, Joint United Nations Programme on HIV/AIDS (UNAIDS)–classified level of HIV epidemic, geographic region, and whether or not injection drug users (IDUs) played a significant role in given epidemic. Pooled ORs were stratified by prevalence level; very low-prevalence countries had an overall MSM OR of 58.4 (95% CI 56.3–60.6); low-prevalence countries, 14.4 (95% CI 13.8–14.9); and medium- to high-prevalence countries, 9.6 (95% CI 9.0–10.2). Significant differences in ORs for HIV infection among MSM in were seen when comparing low- and middle-income countries; low-income countries had an OR of 7.8 (95% CI 7.2–8.4), whereas middle-income countries had an OR of 23.4 (95% CI 22.8–24.0). Stratifying the pooled ORs by whether the country had a substantial component of IDU spread resulted in an OR of 12.8 (95% CI 12.3–13.4) in countries where IDU transmission was prevalent, and 24.4 (95% CI 23.7–25.2) where it was not. By region, the OR for MSM in the Americas was 33.3 (95% CI 32.3–34.2); 18.7 (95% CI 17.7–19.7) for Asia; 3.8 (95% CI 3.3–4.3) for Africa; and 1.3 (95% CI 1.1–1.6) for the low- and middle-income countries of Europe.

Conclusions

MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium–high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.     

Quantifying child mortality reductions related to measles vaccination

Background

This study characterizes the historical relationship between coverage of measles containing vaccines (MCV) and mortality in children under 5 years, with a view toward ongoing global efforts to reduce child mortality.

Methodology/Principal Findings

Using country-level, longitudinal panel data, from 44 countries over the period 1960–2005, we analyzed the relationship between MCV coverage and measles mortality with (1) logistic regressions for no measles deaths in a country-year, and (2) linear regressions for the logarithm of the measles death rate. All regressions allowed a flexible, non-linear relationship between coverage and mortality. Covariates included birth rate, death rates from other causes, percent living in urban areas, population density, per-capita GDP, use of the two-dose MCV, year, and mortality coding system. Regressions used lagged covariates, country fixed effects, and robust standard errors clustered by country. The likelihood of no measles deaths increased nonlinearly with higher MCV coverage (ORs: 13.8 [1.6–122.7] for 80–89% to 40.7 [3.2–517.6] for ≥95%), compared to pre-vaccination risk levels. Measles death rates declined nonlinearly with higher MCV coverage, with benefits accruing more slowly above 90% coverage. Compared to no coverage, predicted average reductions in death rates were −79% at 70% coverage, −93% at 90%, and −95% at 95%.

Conclusions/Significance

40 years of experience with MCV vaccination suggests that extremely high levels of vaccination coverage are needed to produce sharp reductions in measles deaths. Achieving sustainable benefits likely requires a combination of extended vaccine programs and supplementary vaccine efforts.     

Population-attributable risks for ischemic stroke in a community in South Brazil: a case-control study

Background

Risk factors for ischemic stroke are mostly known, but it is still unclear in most countries, what are their combined population-attributable risk percent (PAR%). In a case-control study the individual odds ratios (ORs) and the individual and combined PAR%, including risk factors not addressed in previous studies were estimated.

Methods

Cases and controls were selected from patients attending to an emergency department. Cases were patients aged with 45 years or more with the first episode of ischemic stroke, characterized by a focal neurological deficit or change in the mental status occurring during the previous 24 hours. Controls, matched to cases by age and gender, were selected from patients without neurological complaints.

Results

133 cases and 272 controls were studied. Odds ratios for ischemic stroke were: atrial fibrillation (27.3; CI 95% 7.5–99.9), left ventricular hypertrophy (20.3; CI 95% 8.8–46.4), history of hypertension (11.2; CI 95% 5.4–23.3), physical inactivity (6.6; CI 95% 3.3–13.1), low levels of HDL-cholesterol (5.0; CI 95%2.8–8.9), heavy smoking (2.8; CI 95% 1.5–5.0), carotid bruit (2.5; CI 95% 1.3–4.6), diabetes (2.4; CI 95% 1.4–4.0) and alcohol abuse (2.1; CI 95% 1.1–4.0), The combination of these risk factors accounted for 98.9% (95% CI; 96.4%–99.7%) of the PAR% for all stroke.

Conclusions

Nine risk factors, easily identified, explain almost 100% of the population attributable risk for ischemic stroke.     

The case for reactive mass oral cholera vaccinations

Introduction

The outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal hygiene are ideal for the long term control of cholera, there is controversy about the role of newer approaches such as oral cholera vaccines (OCVs). In October 2009 the Strategic Advisory Group of Experts advised the World Health Organization to consider reactive vaccination campaigns in response to large cholera outbreaks. To evaluate the potential benefit of this pivotal change in WHO policy, we used existing data from cholera outbreaks to simulate the number of cholera cases preventable by reactive mass vaccination.

Methods

Datasets of cholera outbreaks from three sites with varying cholera endemicity—Zimbabwe, Kolkata (India), and Zanzibar (Tanzania)—were analysed to estimate the number of cholera cases preventable under differing response times, vaccine coverage, and vaccine doses.

Findings

The large cholera outbreak in Zimbabwe started in mid August 2008 and by July 2009, 98,591 cholera cases had been reported with 4,288 deaths attributed to cholera. If a rapid response had taken place and half of the population had been vaccinated once the first 400 cases had occurred, as many as 34,900 (40%) cholera cases and 1,695 deaths (40%) could have been prevented. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. A brisk response is required for outbreaks with the majority of cases occurring during the early weeks. Even a delayed response can save a substantial number of cases and deaths in long, drawn-out outbreaks. If circumstances prevent a rapid response there are good reasons to roll out cholera mass vaccination campaigns well into the outbreak. Once a substantial proportion of a population is vaccinated, outbreaks in subsequent years may be reduced if not prevented. A single dose vaccine would be of advantage in short, small outbreaks.

Conclusions

We show that reactive vaccine use can prevent cholera cases and is a rational response to cholera outbreaks in endemic and non-endemic settings. In large and long outbreaks a reactive vaccination with a two-dose vaccine can prevent a substantial proportion of cases. To make mass vaccination campaigns successful, it would be essential to agree when to implement reactive vaccination campaigns and to have a dynamic and determined response team that is familiar with the logistic challenges on standby. Most importantly, the decision makers in donor and recipient countries have to be convinced of the benefit of reactive cholera vaccinations.     

The co-morbidity burden of children and young adults with autism spectrum disorders

Objectives

Use electronic health records Autism Spectrum Disorder (ASD) to assess the comorbidity burden of ASD in children and young adults.

Study Design

A retrospective prevalence study was performed using a distributed query system across three general hospitals and one pediatric hospital. Over 14,000 individuals under age 35 with ASD were characterized by their co-morbidities and conversely, the prevalence of ASD within these comorbidities was measured. The comorbidity prevalence of the younger (Age<18 years) and older (Age 18–34 years) individuals with ASD was compared.

Results

19.44% of ASD patients had epilepsy as compared to 2.19% in the overall hospital population (95% confidence interval for difference in percentages 13.58–14.69%), 2.43% of ASD with schizophrenia vs. 0.24% in the hospital population (95% CI 1.89–2.39%), inflammatory bowel disease (IBD) 0.83% vs. 0.54% (95% CI 0.13–0.43%), bowel disorders (without IBD) 11.74% vs. 4.5% (95% CI 5.72–6.68%), CNS/cranial anomalies 12.45% vs. 1.19% (95% CI 9.41–10.38%), diabetes mellitus type I (DM1) 0.79% vs. 0.34% (95% CI 0.3–0.6%), muscular dystrophy 0.47% vs 0.05% (95% CI 0.26–0.49%), sleep disorders 1.12% vs. 0.14% (95% CI 0.79–1.14%). Autoimmune disorders (excluding DM1 and IBD) were not significantly different at 0.67% vs. 0.68% (95% CI −0.14-0.13%). Three of the studied comorbidities increased significantly when comparing ages 0–17 vs 18–34 with p<0.001: Schizophrenia (1.43% vs. 8.76%), diabetes mellitus type I (0.67% vs. 2.08%), IBD (0.68% vs. 1.99%) whereas sleeping disorders, bowel disorders (without IBD) and epilepsy did not change significantly.

Conclusions

The comorbidities of ASD encompass disease states that are significantly overrepresented in ASD with respect to even the patient populations of tertiary health centers. This burden of comorbidities goes well beyond those routinely managed in developmental medicine centers and requires broad multidisciplinary management that payors and providers will have to plan for.     

Diverging trends in recent population-based survival rates in oesophageal and gastric cancer

Background

Survival trends in oesophageal and gastric cancer need to be updated. A nationwide Swedish population-based study in 1961–2009 was based on registry data.

Methodology/Principal Findings

Relative survival rate, i.e. the ratio of the observed to the expected survival, adjusted for age, sex, and calendar period, and presented with 95% confidence intervals (CI), was the main outcome measure. The expected survival was calculated using the corresponding Swedish general population with no exclusions. The relative survival rates in oesophageal and gastric cardia adenocarcinoma have improved since the 1990s (p for trend <0.001), but not in oesophageal squamous cell carcinoma or gastric non-cardia adenocarcinoma. The relative 5-year survival rates during the two recent periods 1990–1999 and 2000–2008 were 12.5% (95%CI 10.1%–14.9%) and 10.3% (95%CI 8.5–12.0%) for oesophageal squamous cell carcinoma, 12.5% (95%CI 10.1%–14.9%) and 14.6% (95%CI 12.6–16.6%) for oesophageal adenocarcinoma, 11.1% (95%CI 9.6%–12.6%) and 14.3% (95%CI 12.3–16.3%) for gastric cardia adenocarcinoma, and 20.2% (95%CI 19.2%–21.1%) and 19.0% (95%CI 17.7–20.2%) for gastric non-cardia adenocarcinoma. The 3-year survival in tumour stage III in 2004–2008 was about 25% for all four tumour types.

Conclusions/Significance

The survival in oesophageal and cardia adenocarcinoma is increasing, but the lack of such increase in oesophageal squamous cell carcinoma and gastric non-cardia adenocarcinoma is a concern.     

Prevalence of trachoma in unity state, South Sudan: results from a large-scale population-based survey and potential implications for further surveys

Background

Large parts of South Sudan are thought to be trachoma-endemic but baseline data are limited. This study aimed to estimate prevalence for planning trachoma interventions in Unity State, to identify risk factors and to investigate the effect of different sampling approaches on study conclusions.

Methods and Findings

The survey area was defined as one domain of eight counties in Unity State. Across the area, 40 clusters (villages) were randomly selected proportional to the county population size in a population-based prevalence survey. The simplified grading scheme was used to classify clinical signs of trachoma. The unadjusted prevalence of trachoma inflammation-follicular (TF) in children aged 1–9 years was 70.5% (95% CI: 68.6–72.3). After adjusting for age, sex, county and clustering of cases at household and village level the prevalence was 71.0% (95% CI: 69.9–72.1). The prevalence of trachomatous trichiasis (TT) in adults was 15.1% (95% CI: 13.4–17.0) and 13.5% (95% CI: 12.0–15.1) before and after adjustment, respectively. We estimate that 700,000 people (the entire population of Unity State) require antibiotic treatment and approximately 54,178 people require TT surgery. Risk factor analyses confirmed child-level associations with TF and highlighted that older adults living in poverty are at higher risk of TT. Conditional simulations, testing the alternatives of sampling 20 or 60 villages over the same area, indicated that sampling of only 20 villages would have provided an acceptable level of precision for state-level prevalence estimation to inform intervention decisions in this hyperendemic setting.

Conclusion

Trachoma poses an enormous burden on the population of Unity State. Comprehensive control is urgently required to avoid preventable blindness and should be initiated across the state now. In other parts of South Sudan suspected to be highly trachoma endemic, counties should be combined into larger survey areas to generate the baseline data required to initiate interventions.     

Risk factors for ocular infection with Chlamydia trachomatis in children 6 months following mass treatment in Tanzania

Background

Trachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass treatment with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the infectious reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in children post-mass treatment.

Methodology

All children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and household characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection detected by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic regression model was used, accounting for household clustering of children for analysis.

Principal Findings

Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40–4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25–0.80). The age group 2–4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household.

Conclusions

While one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is not sufficient to eliminate infection. Findings that young children (ages 2–4 years) and households with increasing numbers of infected and untreated children have a positive association with infection at 6 months suggest that such households could be targeted for more intensive follow up.     

People with multiple tattoos and/or piercings are not at increased risk for HBV or HCV in The Netherlands

Background

Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in the Netherlands who acquired their tattoos and piercings in the Netherlands and/or abroad.

Methods

Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N = 182), and a biannual survey at our STI-outpatient clinic (N = 252) in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis.

Results

The median number of tattoos and piercings was 5 (IQR 2–10) and 2 (IQR 2–4), respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%–6.46%) participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%–1.29%). Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03–2.75 per 10 years older) and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77–19.7). Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV.

Conclusions

We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries.     

Retention in a NGO supported antiretroviral program in the Democratic Republic of Congo

Background

Retention of patients in ART care is a major challenge in sub-Saharan programs. Retention is also one of the key indicators to evaluate the success of ART programs.

Methods and Findings

A retrospective review of 1500 randomly selected medical charts of adult ART patients from a local non-governmental (NGO) supported ART program in the Democratic Republic of Congo (DRC). Retention was defined as any visit to the clinic in the 4 months prior to the abstraction date. Retention over time and across different sites was described. The relationship between patient characteristics and retention rates at 1 year was also examined. 1450 patients were included in the analysis. The overall retention rates were 81.4% (95% CI: 79.3–83.4), 75.2% (95% CI: 72.8–77.3), 65.0% (95% CI: 62.3–67.6) and 57.2% (95% CI: 54.0–60.3) at 6 months, 1 year, 2 years and 3 years respectively. The retention rates between sites varied between 62.1% and 90.6% at 6 months and between 55.5% and 86.2% at 1 year. During multivariable analysis weight below 50 kg (aHR: 1.33, 95%CI: 1.05–1.69), higher WHO stage at initiation (aHR: 1.22, 95%CI 0.85–1.76 for stage 3 and aHR: 2.98, 95%CI: 1.93–4.59 for stage 4), and male sex (aHR: 1.32, 95%CI: 1.05–1.65) remained as significant risk factors for attrition during the first year after ART initiation. Other independent risk factors were year of initiation (aHR: 1.73, 95%CI: 1.26–2.38 for the year 2007 and aHR: 3.06, 95%CI: 2.26–4.14 for the period 2008–2009), and site.

Conclusions

Retention is a major problem in DRC, while coverage of patients on ART is still very low. With the flattening of funding for HIV care and treatment in sub-Saharan Africa, and with decreasing funding worldwide, maximizing retention during the much needed scaling-up will even be more important.     

Tools to support policy decisions related to treatment strategies and surveillance of Schistosomiasis japonica towards elimination

Background

Appropriate diagnostics to monitor disease trends and assess the effectiveness and impact of interventions are essential for guiding treatment strategies at different thresholds of schistosomiasis transmission and for certifying elimination. Field validation of these assays is urgently needed before they can be adopted to support policy decisions of the national programme for control and elimination of schistosomiasis in P.R. China. We compared the efficacy and utility of different immunoassays in guiding control strategies and monitoring the endemic status of S. japonicum infections towards elimination.

Methodology/Principal Findings

A cross-sectional survey was conducted in seven villages with different transmission intensities settings to assess the performance and utility of three immunoassays, e.g., an indirect hemagglutination assay (IHA_JX), an enzyme linked immunosorbent assay (ELISA_SZ), and a dot immunogold filtration assay (DIGFA_SH). 6,248 individuals aged 6–65 years old who gave consent and supplied their stool and blood samples were included for data analysis. Results showed that ELISA_SZ performed significantly higher sensitivity (95.45%, 95%CI: 92.94–97.97%) than IHA_JX (87.59%, 95%CI: 83.51–91.49%) and DIGFA_SH (79.55%, 95%CI: 74.68–84.41%), especially in subgroups with very low infection intensity. The specificity of ELISA_SZ, IHA_JX, DIGFA_SH in 6–9 year olds with occasional exposure was nearly 90%. DIGFA_SH performed the highest screening efficacy for patients among three assays with overall positive predicative value of 13.07% (95%CI: 11.42–14.72%). We found a positive correlation of antibody positive rate of IHA_JX with results of stool examination in age strata (r = 0.70, P<0.001). Seropositivity of IHA_JX in children aged 6–9 years old showed an excellent correlation with prevalence of schistosome infection in the seven communities (r = 0.77, P<0.05).

Conclusions/Significance

Studies suggest that ELISA_SZ could be used to guide selective chemotherapy in moderate or low endemic regions. IHA_JX could be used to as a surveillance tool and for certifying elimination of schistosomiasis through monitoring children as a sentinel population.     

High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS versus increased risks due to pig-keeping and house construction

Background

African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed.

Methods

Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1–15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed.

Results

Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%–57.1%) in children 1–15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%–27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%–77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR)  = 0.6; 95%CI: 0.4–0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3–0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5–0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0–1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1–4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3–2.4) versus other roofing materials and bigger household size (8–15 people: OR = 1.6; 95%CI: 1.3–2.1) versus small households (1–4 persons).

Conclusion

Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs.