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May 25, 2015

Some thoughts on Dr. Sack's important question on OCV delivery - Part 4 of 6 part series

It is been complete 3 weeks. I came here soon after first big Earth quake hit Kathmandu valley and those Northern  as well Southern hill districts with huge loss of life and infrastructure damage. If we calculate these losses in terms of monetary value, then I think, never before in our history have we suffered so much like in 2015!! However, I found  that we Nepali people are sturdy on close observation. Also, one essence of goodness that we possess is acceptance of "what it is as it is". That means - we have a capacity to accept death and nature's brutality so comfortably. 

During this period of hardship, each of us have to contribute from our position at whatever capacity we possess at individual and professional level. We do understand, immediately aftermath of Earthquake - triage, safety, food, security, injury treatment and efficient management of relief task is always of highest priority, however once time moves forward and healing of acute trauma ensues then there is always our secondary priorities that relates to preparedness of possible infectious diseases outbreak. In this line - I have the same question as raised by Dr. Sher Bahadur Pun, "Are we prepared to respond to  possible outbreaks of infectious diseases?" I know this is such an important question that revolves and strikes different corners of the government mechanism and processes, while in this pertinent threat that Dr. Pun has timely raised also comes the important role of citizens, field of journalism, professionals, opinion leaders and of course - civil society to address and raise concern for preparedness and its action. In this preparatory effort - effective leadership is key so any action taken is timely, focused and evidence based rather than only political. In this light - a senior public health professional said in a casual talk - "You like it or not - public health politics is important and we have to learn to play the game judiciously so we know where we are going and where to act !!" I also think, this is important - key message would be "Politics for better or worse plays a crucial role in health affairs." This is relevant to the public health politics of cholera and its preventive measures. I know, this is a bit rash for some corners involved in this affair of public health policy of implementation and its administration. However, the ground truth is that we all linked up knowingly or unknowingly to web of interests that may be guided by true passion or just of the shake business. For me what count the most is passion of involvement. In this regard, I always stick and commit to the opinion that fruits of science like vaccine for cholera or typhoid fever that are purely developed for the benefit of humanity have to be available to the community. There should be fast track or expedited process for its use or even untangle the administrative web if its use is ethical based on comprehensive safety, efficacy and effectiveness data. 

Going back to the same question that Dr. Sack raised: "How to handle the mismatch between the actual needs and the use of tools available?" This is a challenge that I consider interesting since I foresee solution in near future and that will be based on efficient advocacy and concerted efforts that will bring local government, international partners and most important would be to bring local opinion leaders on board - this will include doctors, civil society and famous figures. Also, I have considered these challenges and mismatch as "a guru" for our learning to negotiate through the climate of uncertainties. Now in Nepal, we are working closely with government in preparedness to respond to possible outbreak should it occur in affected district post earthquake. We are of the same opinion like all learned personalities that Water Sanitation & Hygiene (WASH) strategy is the key approach to control and prevent possible outbreaks of diseases like cholera. However, should the threat outweighs and the risk of outbreak is extremely high in remote areas of the affected districts, then acting upon preemptive vaccination along with WASH measures should be highly considered. No denies this fact and nobody has an intention to go against the prevailing wisdom.This consideration is aligned with the WHO cholera vaccine position paper (2010). Nonetheless, we strongly assert that there should not be any delay in the name of only professional interest that we decide from here in the capital the fate of peoples living in extreme condition due to Earthquake and on top of that, people exposed to extremes of nature's cruelty - landslide, flooding, when monsoon is just a little more than a month away. Understanding the ground situation - myself who also survived cholera / viral hepatitis during younger days, I strongly urge all to think twice how we decide and act for common good at this hour of national distress. Most important point that we hear from everybody on close conversation is the "real" threat of acute diarrheal illness in the remote and high risk areas!! So the relevant question everybody is asking: "Will the outbreak be followed by cholera outbreak in Nepal given the situation that Vibrios cholerae are in circulation and reported in academic journals?" For details, we can read Dr. Lorenzo Von Seidlein, from the DOVE project (www.stopcholera.org) in his PLOS blog post at http://blogs.plos.org/speakingofmedicine/2015/05/21/nepal-after-the-recent-earthquakes-reconstruction-and-vaccine-preventable-enteric-diseases/

May 17, 2015

A short report of suspected Enteric Perforation with localized peritonitis - Post Earthquake (April - May 2015)

On 9th May, 2015 - we went to inspect the temporary settlements in Kamal Binayak, Bhaktapur. We volunteered for few hours to soothe various ailments that local people living there in settlement had to go through. Among various complaints, some had diarrheal illnesses (some acute onset while some suggestive of dysentery), while some senior citizens complaints of joint pain aggravated by cold exposure. I think, there were around 100 to 150 people living there at the time, when we visited the settlement. During that period, we were a bit more concerned with two person who came to the temporary health center established there through District Public Health Office (DPHO), Bhaktapur. One was a middle aged women who was bitten by a local dog. We advised her to visit Sukra Raj Tropical Hospital and informed Dr. Sher Bahadur Pun, who is, I think, one of few passionate doctor in Kathmandu valley. Dr. Pun can be said without doubt one of  a leading infectious disease expert in Nepal. However, we found that she was not taken to Teku hospital for needful further. We know, sometime, local people have other priorities thought to be more important than to get vaccinated. But, we may land into an unfortunate event sometime - rabies is a deadly disease with 100 % fatality. This we know loud and clear! Hope she will be safe and healthy !! 

A child treated for enteric perforation, Bhaktapur (May 2015)
Photo Courtesy:Dr. Bhim Dhoubadel
Other visitor to the temporary clinic in the settlement was a female child of around 10 to 12 years of age. She was brought to the clinic by her parents. On seeing her, I immediately felt "a dead person walking" since she was profusely sweating with her face looking bland and i guess, she was in extreme agony. But she did not express it !! Now, i can realize how much suffering she must have faced hopping from one clinic to another with prescriptions that did not work. Fortunately, Dr, Bhim (Assocaite Professor at Nagasaki University, Japan and also a technical adviser in Sidhi Memorial Hospital in Bhaktapur) examined the child, then immediately diagnosed "intestinal perforation with localized peritonitis" and referred to Sidhi Hospital for surgical exploration. She was provided free care by the hospital and was surgically explored with Intensive Surgical Care. Later we came to know that the child had enteric perforation most probably due to typhoid fever with peritonitis with impending septic shock. She was given pints of blood transfusion. As of now, Dr. Bhim is waiting for reports of blood culture and sensitivity and also biopsy report for the final diagnosis. 

In retrospect, I can think the urgency of this public health problem of typhoid fever in Bhaktapur. We also know and we have been hearing in international forum that Kathmandu valley is considered and reported as "Capital of Typhoid fever". In order to say that there are enough studies to supplement the statement. The only contention that I have to be clear is whether this is exaggeration !! Nonetheless, it is right time that all those involved in the prevention and control of typhoid fever has an excellent opportunity to work in concerted effort to showcase an exemplary public health campaign so we could prevent this enteric illness through vaccination. In this effort to address possible typhoid fever outbreaks that may arise post Earthquake due to compromised water sanitation and hygiene, the Coalition Against Typhoid (CAT) local and international chapters have to act now. Never before has there come this opportunity to advocate typhoid and paratyphoid agenda to the international  fora as an global public health agenda !! I think and i believe, this is immense opportunity that we should not miss and erase once and for all from all literatures and even word of mouth the stigma of "Capital of Typhoid Fever" said for Kathmandu Valley, which is the national headquarter of Nepal. 

May 12, 2015

Some thoughts on Dr. Sack's important question on OCV delivery - Part 3 of 6 part series

Now, it is always in the best interest of community that we talk of the best available options like vaccination early rather than saying "Well this will complicate the situation without understanding the scientific facts as well as merits of vaccinating the most vulnerable during crisis situation. However, we also should acknowledge and prioritize (and can't undermine) WASH measures, which should be employed extensively in the backdrop of disease surveillance, which should be robust in its functioning . Few days ago I read Dr. Sack's blog post in ( www.stopcholera.org ), the key message that I could get from the post is that efficient surveillance and rapid action are the two side of the same coin to stop cholera spreading in the community. This is what all of us emphasize during our conversation with public health colleague here in Nepal. When Dr. Sack says "efficient" surveillance, it also means that it should be equipped with stool sample collection, proper sample transportation, cold chain maintenance and  appropriate lab diagnostic test. In the field however we could use quick diagnostic test like modified rapid dipstick test. This can be supplemented with culture and sensitivity test. Therefore, this is one area, which interests me when assessing the risk of cholera outbreaks in the community and now especially in temporary shelters, where people directly or indirectly affected by Earthquake take refuge for safety. During this temporary stay, I would say children, senior citizens, pregnant women and weak / feeble are at high risk of exposure to various communicable diseases. 

This is so timely, therefore we discuss and put in place robust surveillance and use rapid diagnostic test in 14 affected districts. Once we assess the surveillance data along with risk assessment using appropriate tools available, we would be in a place to take evidence based informed decision. In this light, let me share recent experience of oral cholera vaccination in Malawi where thousands of people were displaced due to flooding. In collaboration with the International Vaccine Institute (IVI), the World Health Organization (WHO) implemented  Oral Cholera vaccination in response to reported and later lab confirmed cholera outbreaks in Psanje, southern part of Malawi . Specifically, WHO provided vaccines for 105000 people while the International Vaccine Institute provided vaccines for 55000 people. The World Health Organization is continuing to lead the monitoring, evaluation and documentation of the best practices in the introduction of the Oral Cholera Vaccine. Also, the mass preventive vaccination were carried out in Guinea, Ethiopia and Haiti.

These are exemplary collaborative efforts to address outbreak caused by neglected diseases that is related to water, sanitation and hygiene in the community. It is unfortunate that we are still lingering with basic necessity that a responsible state has to offer to its people. Because there is lack of such basic utility our people are victim to preventable diseases like cholera. This has become even more relevant when the globe has constricted with rapid transportation (both sea and land) within and outside our boundary. This is further compounded by changing population dynamics as well as climate changes, political instability and rising antibiotic resistance in the community.

While writing this blog, we felt another 7.4 Rector Scale Earthquake with epicenter in Everest region. We do not know as of now, how much it has damaged and loss of life / injuries. We therefore pray that we do not want another Haiti Situation, when cholera outbreak complicated the overall relief and rehabilitation of the state and its people, here in Nepal. We will work in that direction and we are united in this national endeavor. 

Links:
3.       http://www.msf.ie/south-sudan-oral-cholera-vaccination-campaign-maban

May 8, 2015

Post Earthquake Preparedness against possible Infectious Diseases Outbreaks in Nepal

Now I am in Nepal. Today is my 4th day here in Kathmandu. Over these days, I visited key government offices and expressed to directors, "how we can be of assistance to Government of Nepal (GoN)? Also, we stated our competencise, which can be used in case disease outbreaks should occur in Earhquake hit areas. After thorough discussion, my impression (as of now) is that GoN is working hard to address this emergency situation judiciously. The key aspect we need to understand is that the overall coordination of the relief work is being conducted through National Emergency Operation Centre (NEOC), while the health related activities are being coordinated through Health Emergency Operation Centre (HEOC), which are supported by all key international multilateral organizations like WHO, IVI, UNICEF and other UN organization, bilateral organization  and local NGOs and volunteer from many countries. HEOC is spearheaded by Ministry of Health along with other key departments and divisions. Special mention should be Epidemiology and Disease Control Division (EDCD), this division is working hard to control possible infectious diseases outbreaks like cholera, dengue, leptospirosis. To assist GoN, IVI along with WHO, UNICEF, CDC, JHU and GTA (group for technical assistance) is coordinating closely to tackle possible cholera outbreaks in affected districts in Nepal. Key activities that need to be done at the moment are assessment of cholera risk and then present the findings in Enteric Diseases Steering Committee under the leadership of Director General (DG), Department of Health Services. Surveillance is being strengthened and EDCD and WHO are working closely to pick possible outbreaks at the earliest. There is clear directive from the ministry of health to report all reportable infectious diseases SOS without hesitation. GON (at EDCD) along WHO / IVI / UNICEF / JHU / GTA will work hand in hand to mobilise WHO stockpile of cholera vaccine available. 

Key activities that I have been involved as of now:


Relief Camp in Bhaktapur (Photo courtesy Anuj Bhattachan)

5th May 2015: On this day, we had a meeting at EDCD (along with IVI / WHO /GTA). Also, visited WHO Program for Immunization Preventable Diseases (IPD) and Sukra Raj Tropical Hospital, Teku. I met Dr. Sher Bahadur Pun, Infectious Diseases Specialist, who shared his experiences and expressed opinion re: landscape of infectious diseases that report in the hospital. He says that yearly sporadic cases of cholera have been reported in KTM valley.

6th May, 2015: On this day, we had a meeting at Child Health Division (CHD) along with representatives from UNICEF, WHO. In the afternoon, I visited GTA office to prepare concept for tackling infectious diseases outbreaks which is highly possible aftermath of Earthquake in Nepal.

7th May 2015: I had meeting with Rotary Nepal to discuss on IVI Rotary Project that we have planned for Nepal. I also understand, we need to work hard to convince people from different background so we can immunize people from cholera or other vaccine preventable diseases (VPDs) in impoverished community. In the afternoon, we again had follow up meeting at GTA for the finalization of the concept note.

9th May, 2015: I visited Kamal Binayak Camp in Bhaktapur in response to possible cholera outbreak. The key issue after a preliminary report shared by one of senior epidemiologist has created noise among public health professionals involved in surveillance of reportable infectious diseases. The main concern is laboratory investigation of stool samples collected from those camps in the vicinity of Bhaktapur. We hope that the results of the stool examination will be openly shared and acted upon it.


May 3, 2015

3rd day update: 9th International Conference on Typhoid and Invasive NTS disease - Bali, Indonesia

The day started with a symposium on past experience from typhoid vaccine implementation: translating global policy to country use. This was moderated by Kim Mulholland, LSTM, UK. The talk started with Nepal Vi – ps introduction in Nepal. Dr. Pradhan urged international community to assist GON to introduce typhoid vaccine in its national EPI program. The second talk was given by Leon Ochai on vaccine introduction in Pakistan. There was also mention of DOMI program and its relation to assess vaccine effectiveness in the real public health situation with >60 % effectiveness > 5 years of age. It was introduced as school based vaccination. I could see that the coverage was average around 60 %. It was related with trust to the system, the reason for low coverage.
Where do we stand?

  •  Burden of TF – high along with MDR / age of infection as low as 6 months
  • Vaccine use: TF vaccination is efficacious and feasible / capability for vaccinating school children
  • National financial resources limited
  • Global agency financing will facilitate the vax introduction and help in controlling this disease
  • Sri Lankan experience: Jaffna (IDP camps) has the highest incidence of TF followed by Colombo (with highest population) in SL. Vaccine being given to outbreak situation / pilgrims / food handlers / close contact of patients / where water sanitation (poor)/health professional / armed forces / children with frequent of diarrhea. However, there is high literacy / improvement in WSH. There is also environmental surveillance.
  • surveillance – sentinel + lab surveillance
  •  Antibiotic monitoring
  •  Immunization in High risk areas


Conclusion: Government is willing to vaccinate and GAVI is also willing to finance this initiative. We should not hesitate to move forward. Also, we need environmental sampling + improvement in WASH

Integration of TF vaccine in NI Schedule: opportunities and challenges from industry (Bharat Biotech – India). There is higher disease burden in urban so urgent need for its control. (Ochiai + Florian’s paper) Typbar – tcv (6 months and above / single dose / IM – what r the key consideration (WHO ECBS guideline on Typhoid vaccine use)

  • Primary above 6 months / Single dose / at least 6 months of gap for boost / or school based booster
  • Current guidance available NIH efficacy studies
  • New Vaccine Introduction from WHO perspective (Principle, Practices and Realities) -
  • Moving fast

o   Measles vaccination
o   HiB introduction
o   Rubella vaccination
·                     Slow to medium progress
o   JE vaccine – regional vaccine
o   Pneumococccal
o   Rota Vaccine
o   HPV vaccination – cervical cancer

Various scenarios
·         Scenario A - ??
·         Scenario B – low income countries – GAVI funded / sustainability?
·         Scenario C – Gray area / prioritization

Key point to consider – decision making process

·         Burden of disease – various factors (eg incidence / mortality / DALY)
o   Accuracy of the burden studies (syndrome sx may overestimate)
·         Factoring in vaccine efficacy and its effectiveness – looks into overall effectiveness of the vaccine
o   Herd effect / impact
Key message
·         Vaccine effectiveness > efficacy
·         Vaccine factors – age / booster / dosing …..
·         Alternative ways to control also available but for example measles – vaccination is the only option
·         Cost – opportunity cost / cost benefit
·         its priority in government
·         Return on investment
·         Health budget
·         Global agenda (political / global initiative)
Question and answer session
·         what is the vaccine efficacy among 2 to 5 years of age
·         Some voice against using the word ‘alternative” in relation to vaccination e.g. HPV vaccination
·         Typhoid vaccination – John Crump interested with vaccination against frequent in acute diarrheal illness.
·         Breiman – 2 to 5 years of age  vaccine efficacy (factors like fear / poor acceptance might have influenced the low efficacy rate among 2 to 5 years)
·         The effect of taking consent may have an effect on low coverage
·         Dr. Bhutta gave a clear and succinct explanation of why low coverage in Pakistan.
Next symposium is on development of vaccines against typhoid, paratyphoid and NTS. This is the key area where I have an interest. This is moderated by Adwoa Bentsi Enchilli, WHO, Geneva, Switzerland
Ghananian proverb – lesson to be learnt from past
Typbar – TCV (Bharat Biotech, India)
·         Safety and immunogenicity in healthy infants, children and adults in endemic areas
·         control – Typbar (Vi – PS)
·         dose = 0.5 ml / cold chain needed
·         anti Vi igG 6 wks post vaccination – 1 endpoint
·         Safety across 6 months – 45 years
·         Results:
o   safe in all age group
o   Immunogenic (high IgG response) also in < 2 years
o   Persistent in immune response and also memory response
o   antibody avidity is important for qualitative assessment
o   Open label / controlled trial  - TypBar TCV / Typbar
§  Conclusion – safe / immunogenic / immune response persistent < 2 years / booster needed
§  Measles interference study underway
o   My question – Bharat Biotech is way ahead with their conjugate vaccine, how we are going to deal with it as we are working with Vi – DT vaccine


Vi - DT vaccine development – Bio Farma
§  our desire to move from medium > high priority in WHO list of vaccine
§  Target Product Profile (TPP)
§  Process development  / GMP process – master seed and working seed
§  Process flow (Vi Polysachharide)
§  ELISA / NMR /HPAEC method
§  WHO TRS 987 – requirement
§  Vi DT conjugation Process
o   Carrier protein prep
o   Vi PS preparation
o   Conjugation
o   Diafiltration
§  HPLC profile
§  Nonclinical immunogenicity studies (who guideline)
Vi CRM 197
o   CRN
o   Conjugation kinetics as a process map
o   Bulk conjugate vs. Formulated Bulk
o   Study plan – mice study
Live oral vaccine – M01ZH09 (from parent Ty21a with some changes) Ref: Waddington et al, J Infect 2013
o   Vax efficacy / correlates of protection
o   Vaccine efficacy – study design
o   blinded arm (Placebo vs M01ZH09)
o   Open arm (Ty21a)
o   LPS as surrogate of efficacy
o   Then challenge with TF bacteria / diagnosis after challenge (temperature or Blood C/S)
o   Dose escalation study
o   LPS vs. Flagellen vs. Vi
Bivalent Core and O PS (COPS) – flaggelin conjugate vaccine against iNTS and typhimurim infections
o   key - phase 1 flaggellin subunit serves as the carrier protein – target for immune response
Interesting discussion – I guess on emerging considerations for iNTS disease prevention moderated by John Crump, University of Otago, New Zealand
Typhoid conjugate vaccines for public use: overcoming barriers moderated by Zulfiqar Bhutta, University of Toronto, Canada
TF vaccine for public health use: overcoming barriers: moderated by Zulfiqar Bhhutta
o   Current WHO position of TF (2008) – recognition as serious health problem/significant public health burden/local epidemiology/high risk population must be the target/ there are also inadequate data on conjugate vaccine (t cell response / ? young age group)
§  national epidemiological data – rapid assessment tool to map the disease epidemiology (better describe the local epidemiology)
§  Lack of validated assay
o   GAVI – Vaccine Investment Strategy (VIS)
o   2008 HPV/JE / rubella, typhoid conjugate
o   2011 interest in typhoid conjugate
§  WHO PQ and recommendation
§  GAVI program window decision
§  Program implementation
§  Vaccine evaluation
·         vaccination scenarios
·         Demand forecast
·         Develop impact estimates
·         Develop cost estimates
·         Assess other disease / vaccine feature

o   International Vaccine Institute (IVI) -  landscape of what IVI is doing in Vi DT vaccine development
o   Gates Foundation - Stringent and focus / fulcrum of knowledge, innovation and technology / accelerate the product development program (PDP) / focus and ambitious / using the vaccine so we can eliminate it (nationally / regionally)/ integrate vaccine and WSH or other strategies necessary / engagement – innovation so we can address 
o   GAVI process / SAGE – uncertainties re: disease burden – magnitudes / distribution, target age group, strategy utilizing
o   micro planning of deployment – generate evidence / advocacy / once WHO pq we can use it also convince the investors / also generate demand – in direct communication with policy makers so we convince them, prepare ground for deployment of vaccine, guidance of regulatory authorities at country level
o   GAVI – key is evidence / disease burden data – matrix of investment
o   Immunization strategy need to be carved out and political will is also important / political commitment is always need – local champions and translating local data and connecting with policy groups through advocacy and communication
o   Need for efficacy data
o   Lack for good diagnostics so this could help surveillance
o   Transfer of plasmid is on threat??
o   Nepal could advocate strongly in WHA through executive body – how can we move forward???? / Position should focus on implementation part.
o   Global Typhoid Initiative – need

o   description, discovery, development, delivery

2nd day update: 9th International Conference on Typhoid and Invasive NTS disease - Bali, Indonesia

AMR symposium
·         key message is that MDR is an issue with treatment of TF with antibiotic
·         Need for close cooperation to address this problem between clinician and laboratory experts
Genomics and host susceptibility to enteric fever and NTS disease
·         HLA and resistance to enteric fever
o   this is beyond my understanding
o   Key messages:
§  HLA –DRB1+0405 major contributor to resistance
§  May affect antigen presentation
§  T cell response
§  Key individuals in PAHS Salmonella study – Well Come Trust
·         Buddha Basnyat
·         Samir Koirala
·         Sabina Dongol
·         Amit Aryal
·         Abhilasha Karki
Immunity to invasive S infections: lessons from animal models and man
·         System infection progress in distinct phases
o   Innate response
o   Adaptive response (inflammation)
o   T cell dependent acquired immunity
·         “Like a castle cards” – interesting analogy
·         Dynamics of the “in vivo” infection process, immunity and vaccination (thru molecularly tagged or fluorescent)
·         Dispersive infections with intracellular and extracellular phases (analogy - catch me if you can!!)
·         Lessons from Human - vaccines
o   How can we expect the infection with external intervention?
o   Optimize antibody response: isotypes and effector functions
o   Primed cellular response
o   Ab + Cell mediated immunity
o   Epidemiological risk factor vs. susceptibility to disease ( innate immunity and adaptive immunity)
·         Novel insights in host response to understand pathogenesis
o   Typhoid challenge model
o   Waddington et al., CID 2014
o   Cytokines – early response (disappears after 12 hrs)
o   Gene expression after challenge
§  Interferon
o   Cytokines – post response
Typhoid toxin (geno toxin) - Song et al, Nature (2013) absent in non typhoidal Salmonellae
  • Fundamental questions
  • Cytolethal distending toxin + Pertusis toxin

o   Why it causes typhoid fever?
o   Why it only cause disease in humans?
o   a novel toxin and a novel pathway for exotoxin delivery by an intracellular pathogen
o   Salmonella cultured does not produce it??
o   S ty[phi does not survive ……intracellular macrophage
o   Rab 32 / 38 dependent pathway in macrophase  - mechanism of restriction in mice
o   Typhoid organism must have adapted well in humans thru certain sialic acids / glycans
o   Toxin can not affect chimpanzees
o   Deng et al, Cell (in press)


May 2, 2015

First day update - 9th International Conference on Typhoid and Invasive NTS disease - Bali, Indonesia

The first day of the 9th International Conference on Typhpoid and Invasive NTS disease was very interactive. This conference has provided us with a tremendous learning opportunity the amount of work that has been put into understanding Typhoid fever and invasive non typhoid salmonesis.
The day stated with Florian’s (from IVI) talk that provided us the update that include challenges on TSAP project in Sub Saharan Countries. This was followed by Kashimira Date’s talk which also updated on Surveillance of Enteric Fever in Asia (SEFA) project (including in Nepal). I had chance to meet those involved in this project. CDC / GTA along with GON.

Namrata Prasad and  Aaron Jenkins talked on Fiji Typhoid fever study which included case control (CC) study in Fiji, 2014 and another study whose objective was to carve out determinants of typhoid fever in Fiji (multidisciplinary study). The interesting part was the assay work on Soil samples (from houses of cases) and also there was mention of localized behavior / household environments
Questions
  • Urban vs. Rural  (what is the key criteria that differentiate U vs. R)
  •  Geospatial analysis – water supply along with sanitation
  •  Soil sample - how long do the organism last in the soil? (7 to 10 days??)
  • Hand washing – behavior vs. education vs. introduction of bias??
  • Reported vs. observed hand washing practices
  • Does those sites selected (Africa / Asia) really represents the true picture?
  •  Larger geographic sites – could be a greater effort
  • Rapid assessment: cases – from all hospitals / age wise breakdown (? physician’s opinion/survey of sanitation led by governments/spotty / patchy distribution of typhoid fever in Africa (this is what they observed despite good lab facilities)
  • Rapid assessment tool (RAT) - real challenges??
  • Paratyphi
  • 20 % of total Africa population
  • Drug resistance – Ciprofloxacin
  • Vaccine acceptability??

The second session started with a presentation from University of Jakarta on clinical and demographic characteristics of TF in Indonesia. The below are some of the key messages:
  • 64 % TF in 3 – 19 yrs (Indonesia)
  • 3.1 to 10.4% - mortality in hospitalized patients
  • 2nd important infectious diseases
  • Less than 20 liter per day – cut off point

The second and third talks were on mathematical modeling. The first was more focused on the potential consequence of the H58 haplotype of Salmonella Typhii. The following are key messages:
  • Patan Hospital study – KTM Nepal compared to Malawi study
  •  Emergence of H58 haplotype
  • Why is typhoid incidence increasing in Malawi?
  • Bowles CC et al (in prep) – Patan hospital study
  • Infectiousness/ R0
  • usually 4  weeks shedding of bacteria
  • Transmission rate
  • Better diagnostics needed
  • Chronic carrier in the community   
  • ? natural immunity and its role
  •  Influx of susceptible migrant male workers form low incidence rural regions in the country

o   Increasing pop density
o   Cross immunity

The third study was from LSTM / University of Liverpool on modeling in relation to malaria / hiv / malnutrition. While the fourth talk was on Evaluation of a rapid real time molecular assay (S. typhi, paratyphi and S. spp.) from Foundation Merieux, France. The final talk was by Dr. Quadri on Typhoid in Bangladesh: from infection to protection. Some of the key points were on immune response in children (Ty21a) oral route and also about IgA / ALS
Questions:
  • Widal tests
  • Blood c/s

This was also a panel discussion to discuss challenges and approaches in measuring typhoid fever disease burden. The following points were key point discussed:
  •  Research vs. public health mode – what is more important?
  • Generalibility  of what so far we have scientific data
  • Rapid Assessment approach – e.g. used for Pneumo vaccine introduction ( may be based on serology)
  •  It seems – typhoid organism does not survive much in environment!!
  • Shousun Szu – vaccination is important for protection
  • Government’s role and opinion is important
  • Importance of severity study is more study as government policy makers interests in mortality data
  • Policy and global / local investment – data / data / data that represent across geography and age group
  • Partnership across various groups / researchers
  • HiB rat
  • WHO: visibility of the disease – evidence / measures / advocacy


The discussion was followed by symposium on water, Sanitation and hygiene (WASH) interventions for enteric fever control. The key points that were discussed as follows:
  • WASH interventions for enteric fever control ( a ppt. by Standard University)
  • Linking typhoid transmission to the water distribution with water system
  •  main factors for transmission
  •  live change and your risk
  • specific haplotypes circulation and how
  • GPS mapping
  • “Water quality in KTM is poor
  • Typhoid fever, cholera and hepatitis
  • Municipality water supply
  • Surveillance will be the way we will control infectious disease / sort our antimicrobial resistance (AMR) 
  • Why is the H58 lineage so successful? 
  • S. Typhi in the Pacific region are generally island specifics
  • Is this an opportunity for an eradication program?
  • Bring a solution in front of Politician’s nose and hammer it

Anuj in Himalayas

Hi i am connecting disqus with my blog for healthy interaction and open dialogue