H5N1

Diarrhea in 195 countries: A systematic analysis for the Global Burden of Disease Study 2016

Via The Lancet Infectious Diseases: Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. The summary:

Background 

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and aetiologies in 1990–2016 and assesses how the burden of diarrhoea has changed in people of all ages. 

Methods 

We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty. 

Findings 

In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval [UI] 1 244 073–2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894–504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138–155 133) and among all ages (228 047 deaths, 183 526–292 737). 

Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2–85·0), 72·1% (34·0–91·4), and 56·4% (49·3–62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521–2170) could avert one death from diarrhoea. 

Interpretation 

Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention.

Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi

Via The Lancet Global Health: Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal infant mortality in rural communities in Malawi: a population-based birth cohort study. The summary:

Background 

Rotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10–51 weeks. 

Methods 

In this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression. 

Findings 

Between Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1–52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI –28 to 66; p=0·22). 

Interpretation 

RV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes.

MMWR: Three rotavirus outbreaks in the postvaccine era — California, 2017

Via MMWR: Three Rotavirus Outbreaks in the Postvaccine Era — California, 2017. The summary:

What is already known about this topic?  

The introduction of vaccines against rotavirus, the most common cause of severe diarrhea among U.S. children, has substantially reduced disease incidence. 

What is added by this report?  

Rotavirus outbreaks in a child care center and an adult assisted living facility caused primarily mild illness. In a pediatric subacute care facility, illness was widespread and resulted in one death in a toddler with underlying complications. 

What are the implications for public health practice? 

Rotavirus vaccination is most effective against severe disease. Vaccination reduces transmission and might confer indirect protection to unvaccinated individuals, but outbreaks will continue. Public health practitioners and clinicians should consider rotavirus in cases of acute gastroenteritis and promote rotavirus vaccination per CDC guidelines.

China: Serious flu and other outbreaks in Yangzhou

Via FluTrackers, Sharon Sanders posts an unedited Google translation from a long report in the Yangzhou Times: China - "This year's flu is the fiercest in recent years, with a long duration and a wide area of ​​infection.." Excerpt and then a comment:

It is reported that currently there are five major virus rampant, namely, influenza virus, Norovirus, rotavirus, adenovirus, syncytial virus, influenza virus most likely to cause respiratory infections; Norovirus and rotavirus can cause vomiting in children And diarrhea, while adenovirus can cause diarrhea in children. Syncytial virus, it will cause children fever, bronchitis, pneumonia, myocarditis and so on.

Q: Why are so many children more recently?

A: The flu season, and the weather 　　

Chen Xiao analysis, on the one hand, this and the recent weather changes. Dry weather in winter, will stimulate the respiratory tract, leading to the human body to the outside world the resistance of the virus decreased, some time ago the weather is colder, the temperature has picked up these days, a cold and heat, weak immune children are particularly vulnerable to cold; the other It is also the popular season for influenza virus. Both have caused the current peak. 　　

"This year's flu is the fiercest in recent years, with a long duration and a wide area of ​​infection, which have not been experienced in recent years." The reporter interviewed pediatric experts from other hospitals and learned that with the opening of the second child policy, It is also a factor that has dramatically increased the number of outpatient and emergency department visits in pediatrics.

Despite the inevitable garbling of a Google translation from Chinese to English, the full report indicates that Yangzhou hospitals are swamped with sick kids. I'll try to find out if other Chinese cities are reporting similar problems.

Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger

Via NEJM, perhaps the best news of 2017 so far: Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. The abstract and then a comment:

BACKGROUND 

Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.

METHODS 

We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. 

RESULTS 

Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.

CONCLUSIONS 

Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000.)

Yet another reason why I'm happy to donate monthly to MSF. For a news report on this finding, see The New York Times.

Now the trick will be to provide millions of rotavirus survivors with something like a life.

Hong Kong: CHP appeals for vigilance against acute gastroenteritis

Via the Centre for Health Protection: CHP appeals for vigilance against acute gastroenteritis. Excerpt:

The Centre for Health Protection (CHP) of the Department of Health (DH) today (March 15) drew the attention of the public and management of schools and institutions to the prevention of acute gastroenteritis (AGE) by maintaining personal, environmental and food hygiene in view of the recent increase in AGE activity locally. 

According to the latest surveillance data, the number of institutional AGE outbreaks rose from three (affecting 28 persons) in the week ending February 25 to 12 (affecting 132 persons) in the week ending March 11. As of yesterday (March 14), five outbreaks (affecting 46 persons) had also been reported this week. Most of the recent outbreaks occurred in kindergartens and child care centres.      

In addition, the DH's sentinel surveillance based at General Outpatient Clinics and child care centres/kindergartens also recorded corresponding increases in AGE activity.      

"AGE, commonly caused by norovirus and rotavirus, is a frequent cause of outbreaks in schools and institutions. AGE outbreaks may occur throughout the year but are known to occur more frequently in winter. AGE is highly infectious and may result in outbreaks which are difficult to control," a spokesman for the CHP said.      

"We have issued letters to doctors, hospitals, institutions and schools today on the latest situation. Schools and institutions are also reminded to follow the Guidelines on Prevention of Communicable Diseases on preventive and control measures as well as management of outbreaks, which should be reported to the CHP for prompt follow-up. Health advice has also been given," the spokesman said.

ECDC: Expert opinion on rotavirus vaccination in infancy

ECDC has published Expert opinion on rotavirus vaccination infancy: public consultation opens. Excerpt:

​Each year, an estimated 75,000-150,000 children aged under five are hospitalised in the EU/EEA due to rotavirus disease, according to burden of disease studies conducted in eighteen EU/EEA Member States. Mortality rates are low due to easy access to adequate medical treatment. Children seeking medical attention with rotavirus disease in emergency departments/out-patient settings or those hospitalised have the potential to be sources of nosocomial infection in other children attending medical services.  

In 2006, two live attenuated rotavirus vaccines for oral use in infants were authorized for prevention of rotavirus disease in the EU. Vaccine effectiveness documented in observational studies when the vaccines have been introduced into routine paediatric vaccination programmes ranges between 85-90%. Inclusion of rotavirus vaccines in the routine childhood immunisation programme has been initiated or will soon be initiated in 12 EU/EEA countries. 

ECDC is launching for public consultation an expert opinion on rotavirus vaccination in infancy. 

The final expert opinion aims to provide EU/EEA Member States with relevant scientific information and expert opinion to support the decision-making process on the possible introduction and monitoring of routine vaccination of infants against rotavirus-induced gastroenteritis.  

The expert opinion highlights issues to be considered before and after introduction of rotavirus vaccines, and identifies knowledge gaps and areas in need of further research.  

In order to receive comments from the scientific community and other stakeholders, the expert opinion is open for public consultation. The deadline for submission of comments is 28 November, 2016. 

WHO on World Immunization Week 2016: Immunization game-changers should be the norm worldwide

A news release from WHO: World Immunization Week 2016: Immunization game-changers should be the norm worldwide. Excerpt:

During World Immunization Week 2016, held 24-30 April, WHO highlights recent gains in immunization coverage, and outlines further steps countries can take to “Close the Immunization Gap” and meet global vaccination targets by 2020. 

“Last year immunization led to some notable wins in the fight against polio, rubella and maternal and neonatal tetanus,” says Dr Margaret Chan, WHO Director-General. “But they were isolated wins. Polio was eliminated in 1 country, tetanus in 3, and rubella in 1 geographical region. The challenge now is to make gains like this the norm.” 

Immunization averts 2 to 3 million deaths annually; however, an additional 1.5 million deaths could be avoided if global vaccination coverage improves. Today, an estimated 18.7 million infants – nearly 1 in 5 children – worldwide are still missing routine immunizations for preventable diseases, such as diphtheria, pertussis and tetanus. 

In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP), a commitment to ensure that no one misses out on vital immunizations. Despite gains in vaccination coverage in some regions and countries the past year, global vaccination targets remain off track. 

Global Vaccine Action Plan 2011 - 2020

Only 1 out of 6 targets is on track — the introduction of new or underutilized vaccines in low- and middle-income countries. During the past 5 years, 86 low- and middle-income countries have made 128 introductions of the following vaccines: Hib-containing vaccine, pneumococcal conjugate vaccine (PCV), rotavirus vaccine, human papillomavirus vaccine (HPV), rubella and inactivated polio vaccine. The target is to introduce 1 or more new or underutilized vaccines in at least 90 low- and middle-income countries by 2015.

Dr. Oxford on Ebola as an aerosol virus

Thanks to Irene L for tweeting the link to this important post at International SOS Ebola: comments on Ebola as an aerosol virus by Professor John Oxford. Excerpt:

A key virological fact to remember here is that we are dealing with vast populations of Ebola as much as 10 million viruses per micro drop of diarrhoea. These early observations have been well confirmed in the current outbreak. Of necessity with this way of spreading then the number of cases in the community will remain very low and the chain of infection will be easily broken by quarantine of suspects, training of medical staff in Personal Protective Equipment (PPE), good hygiene and a ‘no touch’ technique at funerals of victims and in the community. Evidence from most outbreaks as well as the present one amply confirms this. 

As regards the numerical issue, we have to date around 21,000 cases in 12 months in a population of 30 million or so in the countries involved. These are relatively low numbers indeed and do not speak to us of aerosol or air droplet spread. 

To give a contrary example of droplets and aerosol spread, in the last week a cornucopia of respiratory viruses have struck in the UK such as influenza, RSV and adenovirus, all spread mainly in the airborne manner and 100,000 persons have been infected over those few days. 

I also want to widen the context to other viruses to illustrate that under very special circumstances these minute viruses can take advantage of a unique or unexpected opportunity to spread. We all know that hepatitis B is at a relatively high level in Africa and is spread by sex, blood and birth. 

But in an overcrowded family household with lots sharing of towels, toothbrushes and shaving kits, even in the observed absence of blood, the virus can spread. This happens in the UK as well. The reason? The virus, like Ebola, is present in the victim in exceedingly high numbers of greater than 10 million viruses per micro drop of blood. 

We never begin to speculate with hepatitis B that it could be spread by coughing, although I have little doubt that amongst the 200 million or so carriers in the world such a transmission has occurred! The virus would certainly be present in mouths with poor tooth hygiene. 

Even more relevant is polio. The spread here is faecal/oral via sewage contaminated rivers, swimming pools or, in the family, by poor hand hygiene. But many of the early studies with the live attenuated polio vaccines described the presence of polio virus in saliva from the throat. So again we have well established and documented manner of spreading of a virus by the faecal/oral route, but it is never thought that polio could be spread by coughs and sneezes. 

As a final illustration of the ‘just possible’ is rotavirus. This important diarrhoea virus, which incidentally would be expected to have killed more children in West Africa during the last year, compared to Ebola, is again present in stools in exceedingly high quantities. So should a mother casually throw a diarrhoea nappy [diaper] onto the table a few virus particles could spray out as droplets and it is possible that these could be breathed in. 

As regards the ‘catch all’ that RNA viruses can mutate, most they do not and the exceptions are influenza and HIV. Polio, rubella, measles, mumps to name a few have not changed in 60 years and Ebola is the same. 

Post peak infection curves of the virus always carry a danger 

The curve of acquisition of new cases of Ebola, along with figures of death, had peaked in Liberia and Guinea  before Christmas: shortly before the arrival of many international groups. This does not mean that their help was unneeded. The contrary is definitely the case. The withdrawal of these trained medical and nursing staff at this precise moment would not be helpful. 

The downward running curve of Ebola cases is exceedingly dangerous for two reasons. Firstly the medical staff will be refocused on the other infections in West Africa, malaria, Lassa fever, cholera and enteric pathogens and TB. The declining Ebola cases will make them more easy to miss. 

Even more important, these communities themselves will begin to relax and touching and kissing, and funeral habits will start up again. 

It took one year to go from one case to 21,000 but now we are not at ground zero with the number of persons currently infected and so outbreaks could start up again from figures way above one! West Africa needs our scientific and medical help for at least the next 6 months and thereafter to train staff for the next outbreak.

Dr. Oxford concludes by writing: "...what these three West African countries really need is international help to build safe water system, sewage, and a health service with well trained doctors and nurses fit for the 21st century. Is this beyond the pale in a world where 500 young people in Europe have volunteered in the last few days to go to Mars on a one way ticket?"

Potential advance in preserving vaccines

Via The New York Times: Preserving Vaccines. Excerpt:

Scientists studying microbes that live in volcanic hot springs have invented a way to preserve viruses that could someday change how vaccines are delivered in poor countries. 

Much work remains to be done, but an intriguing study in The Journal of Virology describes how Portland State University scientists prevented several viruses from drying out by coating them with silica, the basic ingredient of glass, just as they are coated in hot springs. Once the silica coats were rinsed off, some of the viruses were able to infect cells again. 

Most vaccines are made of weakened virus or viral bits, and many need refrigeration. Keeping them cold is a major challenge when it comes to protecting children living in villages without electricity. 

“It’s hard to put a fridge on the back of a donkey,” said Kenneth M. Stedman, a biologist at Portland State and the lead author of the study. 

By recreating the chemical-laden hot-spring environment, Dr. Stedman’s team coated four types of virus with silica, stored them, then washed off the silica and tried to infect cells. One heavily studied virus, phage T4, which infects the cells of E. coli bacteria, retained 90 percent of its infectivity for almost a month. The virus used in smallpox vaccines also did well, but it is naturally able to be stored dry. 

The team is now testing the technique on harder targets: flu virus and rotavirus, which can cause fatal childhood diarrhea. “And we’re definitely interested in polio,” he added.