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Jun 26, 2015

Random thoughts on public health politics - Part 6 of 6 part series

In my previous post dated 21 June 2015, I expressed a deeper insight into what goes on and what we are not able to understand the web of public health politics. Here again, I would like re iterate that I am not able to say certainly what goes in the mind of decision makers at the international headquarters, but at least i can say - we understand the pulse of "what goes on" and "how it goes" in our local community !! Sometime, however - we are cognizance of the fact that we may subjectively feel that whatever we said and did should be right but we may not be up to the mark and fail to realize this fact !! It is therefore necessary that we need to analyse retrospectively what we do and how we think so we do not make the same mistake again and again. Time and then to keep us sane in times of confusion timely reading stories on infectious diseases gurus like Brad and David Sack encourages us to move forward in what we aspire to do. We also get encouraged to work hard and perspective in what we envision doing  in countries like Nepal.

Yesterday, I had to go through a psychological test (not in a psychiatrist or psychologist' chamber) at a personnel level. So you may ask what is this test and what does it have to do with public health politics. Well - it is about your ability to express your ideas (both at academic, programmatic or even anger or frustration)  in coherent manner. Sometime I have begun to question - does your language of expression to express your thought or ideas have any relation with public health politics or it is more than the language of expression - calculating the equation or even deciphering the intricacies in the relation that sometime exist beyond our knowledge? I know I am asking a very personal or even complex question. When in a national or even international forum - i had to face frequently the linguistic gap many of times. For example - my mother tongue is Thakali and all my childhood - i had to work hard to excel Nepali language and to be competent enough to understand science we had to learn English as one of the main foreign language. I do not want to each and every detail however I would be vocal and straight that we have to face challenges while writing and expressing our thoughts in the language other than our mother tongue !! Do you believe what I am saying? May be you may say - Oh this guy is being too emotional and ranting blah blah..... but this is one of my experience at deeper level after years year of trying to understand why we could not excel in some of the subjects that we had to learn in either Nepali or English !! I found the answer and this is definitely  language related competencies !! Along with it are its trailing competencies such as communication skills and also emotional or even social skills. And sometime - we get cornered just because we are not able to express what we think clearly in the language other than our own language. Do you agree with me?? Well, you do not have to agree with me but those who have to go through this subtle difficulties faced in their daily affairs may agree with me completely or partially. Again, you may ask, what does this language competencies or even communication skills have to do with public health politics? Well, this has a big role - and as I said I felt it acutely when approaching in such forum where you have to express your thoughts. 

Expressing all these thoughts at random - I would definitely say "Public Health Politics" has many dimensions and its equation has many variables. Among those variables - i would say language competency is the most important one. In some of the conference - we see those who can express their thoughts coherently, loud and vocal are able to bring their agenda in the forum and bring about impact in the conversation. This will, in turn, help them shape their idea through policy / decision bodies. That is why we have a Nepali proverb, " Those who speak loud and clear can sell even an item of no value, however those who do not speak can't even sell "rice" !!" With this proverb - let us start being vocal but also understand the landscape of public health politics, which is always fluid and changing within time and space - uncertain !! 

27th June 2015
 Kathmandu

Jun 20, 2015

Random thoughts on OCV delivery and public health politics in Nepal - Part 5 of 6 part series

By the time I am writing this blog post - my stay here in Kathmandu has crossed 45 days. The reason that I am here in Kathmandu was and is to be the part of greater Nepali family, which is what I have deeply felt from the beginning. I have never before felt this deep sense of solidarity than now to our own community, relatives, friends and people from all walks of life. This is an interesting "feeling" or "perception" which I need to fathom deeper and I guess, this is the kind of "togetherness" that we need to inculcate in our society.  Well, to put aside this soft feeling that I can hear and experience around us, we also have been the victim of "invisible hands" in what we do and what we want to do !! Myself, who was raised and brought up in rural community far away from "comforts" of urban city like Pokhara and Kathmandu, is not enough of "stories" to convince decision makers in the authority - it required more than that. "That" would be public health politics and we need to be master at it. 

Forget - big super cities !! We know how our people in the rural communities still have to suffer from malnutrition, worm infestation, common preventable diseases that have already been eliminated from high or even middle income countries. We know surveillance of these preventable diseases have to be robust supplemented by lab diagnostic facilities, while I am sorry this is still a challenge and too primitive in remote hard to reach areas of our country. Yes we know that there is such system in paper and public health leaders are cognizance of this scenario. It is not that they are unaware but these leadership are not able to enforce such surveillance in remote areas due to various bureaucratic red tape and of course, lack of "much needed" human as well as logistics resources. We also know that just observing and experiencing these diseases or even the systemic challenges in the community is not enough - what we need is evidence and that too in writing thoroughly supported by data available. However, I think - the availability of such data can be challenging in times of public health crisis or emergencies like Earthquake and Nepal's recent event is an example. 

Now, a little disconnection from above trail of thoughts - for me 45 days has been just like 5 to 15 days only - what a amazing experience so far !! Here I also like to share  - Nepal is a wonderful place to work and Nepalese are resilient people to be with. Also, I have to be straight and vocal - we are sometime disillusioned without clear goals and road map buried in our own mountain of problems created out of complacency or too many heads working like "too many cooks spoils the broth"!! Sometime in the future - I need to write this amazing experience in writing or at least as an essay.

Coming to back to topic of my post - during this 45 days period (my focused goal here in Nepal is to vaccinate the most vulnerable population) - I did not think in depth the complex processes that were in play when were working hard to mobilize oral cholera vaccine (OCV) in preparedness for preventive vaccination in heavily affected districts and that too not the whole districts but only selected villages at the highest risk. We are still trying to get the vaccine but we are not sure whether we will get the vaccine although we are prepared for the conduct of campaign. We are aware of the "seen" and "unseen" challenges that we have to face. We are prepared to accept a scenario where we are rejected from getting the vaccines. Another - to facilitate the process that we get the vaccines, we are doing our best to coordinate with all concerned and most of the partner organizations are positive except one or two organization who have reservation and we are trying our best to bring those organization on board. Somebody senior public health specialist, whom I respect a lot in his extra ordinary skill to make things happen, uses the term - "public health politics". I agree - it is more than just science and its technicality. It is however the "damn" shrewd coordination that works well if we are able to understand the "bigger picture" and landscape of interest groups in the picture. Our big picture that we know is " to protect the community through integrated preventive and control measures against enteric diseases like cholera, typhoid fever, HEV etc." As of now, our communities in the rural areas are coping well with the loss and structural damages while many children, women and weak and old are vulnerable to infectious diseases especially water borne illness, which could spread should there occur trigger factors of poor water, sanitation and hygiene. We also have to remember that Nepali humanitarian peace keeping forces were pointed out as the carrier of cholera bacterium in Haiti on record. It is therefore we want to prevent the possibility of cholera outbreak at the earliest before the monsoon starts. But we fear, time is the essence and my pnly question - are we entangled with unnecessary processes or "ego" or "arrogance" that emanates at personal level but not at organizational level? This is too tough to understand however the only caution that I am vocal about "No Jajarkot Cholera tragedy again!!" 

21 June 2015
Kathmandu

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 one denies this universal 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 professional interest or I would call it in literal meaning "compartment syndrome" 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)


Anuj in Himalayas

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