UGANDA/SOUTH SUDAN: Nodding Syndrome - Hundreds of children infected

[Pathfinder]

Re: UGANDA: Nodding Syndrome - Hundreds of children infected

Nodding disease children flown to US for a study

By Agatha Ayebazibwe
Posted Wednesday, May 14 2014 at 01:00

A group of family members affected by the nodding syndrome has been flown to the US for a genetic study, according to the ministry of Health.
...
The cause of the disease remains unknown years after it was first diagnosed in Lamwo District ? Acholi sub-region in 2009.

Dr Ruhakana Rugunda, the minister of Health said 10 people, some with the nodding syndrome and others without it, will spend a week at the National Institute of Health in Washington, US to provide sample for the study.

The six-month study will be conducted in collaboration with Uganda?s ministry of Health, Centre for Disease Control US and Makerere University School of Public Health.
...

http://www.monitor.co.ug/News/National/Nodding-disease--children-flown-to-US-for-a-study/-/688334/2313576/-/j0x4xcz/-/index.html

[Emily]

Re: UGANDA: Nodding Syndrome - Hundreds of children infected

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557692/

Clinical and epidemiologic characteristics of nodding syndrome in Mundri County, southern Sudan
JK Tumwine, K Vandemaele, S Chungong, M Richer, M Anker, Y Ayana, ML Opoka, DN Klaucke, A Quarello, PS Spencer
Afr Health Sci. 2012 September; 12(3): 242?248.

PMCID:
PMC3557692
...

A history of measles was negatively associated with being a case: 2/13 of cases and 11/19 of controls had had measles: odds ratio 0.13 (95% CI 0.02, 0.76).
...
Possible differences in measles vaccination history among cases and controls were not determined.

SSPE pretty much ruled out:

http://www.ajol.info/index.php/ahs/a...ew/93455/82881
Nodding syndrome in Mundri county, South Sudan: environmental,
nutritional and infectious factors
*Spencer PS1, Vandemaele K2, Richer M3, Palmer VS4, Chungong S5, Anker M6, Ayana Y7, Opoka ML8, Klaucke BN9, Quarello A10, Tumwine JK11
...
Measles infection in infancy increases the risk
for the subsequent development of subacute measles
encephalitis (incubation 5-6 months) and subacute
sclerosing panencephalitis (SSPE), a rare (1/100,000)
progressive neurodegenerative disorder that has been
reported to cause cognitive changes and head
nodding on awakening.127 Onset of SSPE occurs 1
month to 27 years (mean 7 years) after a primary
systemic measles infection; others report a 2-10 year
silent period.128 The onset is insidious, with
progressive deterioration of behavior and intellect,
followed by ataxia, myoclonic seizures, and death
within 2-3 years.126 We did not screen for SSPE in
our cases and controls, but negative findings for SSPE
have been reported in Ugandan children with
Nodding Syndrome.64

So why does having had natural measles appear to confer protection and what does that protect from?

http://www.sciencedirect.com/science...87760499000765

[alert]

Re: UGANDA/SOUTH SUDAN: Nodding Syndrome - Hundreds of children infected

I can think of a few reasons why nodding syndrome patients would be less likely than the general population to have had measles. The obvious one is that measles in a nodding syndrome patient might have a fairly high acute fatality rate, so those children aren't alive to study.

Alternatively, nodding syndrome patients are often kept at home, due to their disability, so they are unlikely to encounter a number of communicable diseases, simply by their lack of human contact, especially with other children.

The only conclusion I would draw from that fact is the nodding disease is unlikely to be SSPE.

[Emily]

Re: UGANDA/SOUTH SUDAN: Nodding Syndrome - Hundreds of children infected

http://www.mediacentre.go.ug/press-release/press-statement-progress-nodding-syndrome-interventions

PRESS STATEMENT ON THE PROGRESS ON NODDING SYNDROME INTERVENTIONS

MINISTRY OF HEALTH

13/05/2014

Ruhakana Rugunda (Dr)
Minister for Health.


PRESS STATEMENT ON THE LAUNCH OF

PRESS STATEMENT ON THE PROGRESS ON NODDING SYNROME INTERVENTIONS

...

Autopsy Study
Five brain samples collected at various intervals from the several treatment centers were flown to Atlanta last month, April 2014, for analysis. Four were samples from nodding syndrome cases while one was from an epileptic case. Three of the four nodding cases were found to have identical lesions in the same region of the brain. The fourth nodding case did not present like the other three. The epileptic had no brain lesions at all. Further tests are ongoing to ascertain the cause of these lesions
Genetic studies
10 people from a nodding syndrome family were last Saturday flown to the National Institute of Health, (NIH) Washington to undergo genetic studies. The objective of this study is to help us understand whether there is a genetic basis as a cause for nodding syndrome and why it affects some and not all in a given family. - See more at: http://www.mediacentre.go.ug/press-r....MzKKFDHb.dpuf

Dysbalanced Immune System in Cryptogenic Lennox-Gastaut Syndrome

Different neurophysiologic patterns of myoclonus characterize Lennox?Gastaut syndrome and myoclonic astatic epilepsy

P Bonanni, L Parmeggiani, R Guerrini - Epilepsia, 2002 - Wiley Online Library
... image. Myclonic?astatic epilepsy. Clinically, myoclonic seizures were symmetric, involving arms
and shoulders, with head nodding, sometimes leading to falls. ... Beaumanoir A, Dravet C. The
Lennox-Gastaut syndrome. ... Epileptic syndromes in infancy, childhood and adolescence. ...
Cited by 24 Related articles All 5 versions Cite Save

The problem of the Lennox syndrome

J Aicardi - Developmental Medicine & Child Neurology, 1973 - Wiley Online Library
... the large majority of cases fitting the clinical concept of the Lennox-Gastaut syndrome but also
a ... those who are primarily concerned with the clinical aspects, the term 'Lennox syndrome' will
be ... These clinical features are: (1) head-drop attacks or head- nodding spells, whatever ...
Cited by 52 Related articles All 3 versions Cite Save

[Pathfinder]

Four Gulu children die of nodding disease

By Cissy Makumbi

Posted Wednesday, October 7 2015 at 01:00

Gulu. Four children suffering from the nodding disease syndrome in Gulu District have died in the last two months due to lack of drugs.

The focal person for Nodding Syndrome, Mr Michael Cankara, said last Monday that lack of drugs has affected recovery of 226 children in the area.

?Failure to have the drugs in place has been a setback in the recovery of the children. We have so far lost four of them due to lack of drugs,? he said.
...

http://www.monitor.co.ug/News/National/Four-Gulu-children-die-of-nodding-disease/-/688334/2901420/-/gogeyh/-/index.html

[Emily]

Here's a recent study that shows some promise for immune treatments, (correction of a B vitamin deficiency was also done), to slow seizure activity based on a theory that nodding syndrome is an autoimmune disorder after prior onchocerciasis infection:
http://www.neurology.org/content/84/.../S37.005.short

Another study shows how the illness could appear during times of food stress or pesticide exposure:
http://www.neurology.org/content/84/...t/P2.321.short

Eating emergency food [OR=4.0 (1.3-12.4), P=0.0162], moldy maize [OR=4.0 (1.0-16.0), P=0.0496], emergency red sorghum [OR 2.4 (0.9-6.5), P=0.0848], and (pesticide-coated) painted seed [OR 2.3 (0.9-5.8), P=0.0696], was more likely in cases than in controls. CONCLUSIONS: Exposure to plant components with chemical substances of natural origin (mycotoxins) and synthetic origin (pesticide) are possible risk factors for NS in northern Uganda.

[Emily]

http://allafrica.com/stories/201512210390.html

Uganda: Nodding Syndrome - Could Weapons in Wars Have a Link to the Disease?
Opinion By Tabu Butagira and Emmanuel Ainebyoona The disease mostly affects children aged 5-15. Its victims suffer sporadic seizures, drip saliva and nod uncontrollably.
Dozens have died; hundreds dropped out of school, while thousands are confined at home, with some restrained from possible self-inflicted harm by tying them in the courtyards as family members go farming or for other chores.
Residents have been alarmed and mystified, the government stranded. Now science is unraveling the mystery, but not giving the ultimate solution.
Victims of the Nodding Syndrome have excessive accumulation of fat in their brains, findings at Centers for Disease Control and Prevention (CDC) laboratories in the US show.
The crystal substances that CDC experts in 2014 observed in brain samples of the patients, dissolved when stored in alcohol, leaving what the scientists call "holes".
"These 'holes' do not contain appreciable polarisable crystals that were observed in the first batch samples," the scientists note in a new three-page report following a second round of tests at CDC laboratories in Atlanta, Georgia.
...
The previous samples had been stored in formalin in transit to the US, and the CDC this year compelled Ugandan scientists to adhere strictly to the Centres' protocol by storing the samples in alcohol before and during delivery to Atlanta.
The crystal substances, seen in both the 2014 and this year's samples, dissolved when moved from formalin to alcohol.
"We suspect it is abnormal fat depositions in the brain, but this is inconclusive. We will need more investigations to get to the bottom of the still mysterious illness," Dr Sylvester Onzivua, one of the Ugandan pathologists involved in the study, said in response to enquiries by this newspaper.

...
Scientists are also evaluating whether the Nodding Syndrome, observed in Tanzania in 1962 and lately more widespread in South Sudan, might be caused by tetramine poison associated with some toxic plants, vaccines and chemical weapons.
Both northern Uganda, which is afflicted by the disease, and its neighbouring South Sudan, are post-conflict communities; raising suspicion the weapons used in the wars could have a link to the disease....

There are tetramine compounds used as rat poisons, medicines, and weapons. Also a compound called 'hexamethylenetetramine' used as a preservative and in solid fuel for emergency relief situations. Children get exposed to toxic fumes and smoke from heating and cooking in refugee camps.

[alert]

Published Date: 2017-02-18 10:32:53
Subject: PRO> Undiagnosed cerebral disease - Uganda: nodding disease, autoimmune reaction
Archive Number: 20170218.4848145
UNDIAGNOSED CEREBRAL DISEASE - UGANDA: NODDING DISEASE, AUTOIMMUNE REACTION
************************************************** *************************
A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

Date: Wed 15 Feb 2017
Source: Science Translational Medicine [edited]

http://stm.sciencemag.org/content/9/377/eaaf6953

Nodding syndrome [NS] may be an autoimmune reaction to the parasitic worm _Onchocerca volvulus_. Johnson TP et al. Sci Transl Med. 2017 Feb 15;9(377). pii: eaaf6953. doi: 10.1126/scitranslmed.aaf6953.

Abstract:
Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with _Onchocerca volvulus_, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive.

We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome.

Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with _O. volvulus_ antigens.

This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with _O. volvulus_ antigens and suggests that patients may benefit from immunomodulatory therapies.

--
Communicated by:
ProMED-mail


[Nodding disease syndrome has remained enigmatic since the 1st link to Onchocerciasis was proposed in 1992 and 1994:
"(Kipp W et al. (1994) Onchocerciasis and epilepsy in Uganda. Lancet 1994;343:183-4; and Kipp W et al. Improvement in seizures after ivermectin. Lancet 1992;340:789-790)."

This is the 1st study to report a biological marker and to provide a plausible biological explanation for NS. The results are in line with a previous study finding a link between onchocerciasis exposure, lack of ivermectin treatment and NS (Risk factors for epilepsy in Bas-Uele Province, Democratic Republic of the Congo: a case-control study. Colebunders R et al. Int J Infect Dis. 2016 Aug;49:1-8. doi: 10.1016/j.ijid.2016.05.018. Epub 19 May 2016 https://www.ncbi.nlm.nih.gov/pubmed/27210267). - Mod.EP

[Pathfinder]

https://en.wikipedia.org/wiki/Maridi_State

South Sudan

EYE RADIO NEWS & NOTEWORTHY, HEALTH, STATES

Maridi records more nodding disease cases

Hellen Achayo | August 9, 2017 | 8:42 am

At least one hundred and five cases of nodding syndrome have been confirmed in Maridi state, health authorities have announced.

This is about 50 percent increase since the disease was reported 2 months ago.
...
?Some months back the team managed to screen at least 265 patients. From these 265 patients, 105 of them are confirmed cases of nodding syndrome.?
...

http://www.eyeradio.org/maridi-records-nodding-disease-cases/

[Pathfinder]

Coming face-to-face with nodding disease

November 9, 2017 Written by Joseph Kimbowa
...
Layet is one of 15 children suffering from nodding disease in Augustine Ocitti?s household in Okidi Central in Labongo Amida sub-country of Kitgum district.

According to Lam Kanuela, a woman councilor from Amida, this sub-county has the biggest concentration of nodding syndrome patients in the country.

Okidi Central alone has 56 registered cases of nodding disease of the more than 270 cases in the district.
...
A laboratory was set up at Kitgum hospital last year to conduct further research on this mysterious disease but there has been no breakthrough.

Residents now rely on help from various non-governmental organisations that occasionally distribute food items to these children. But this is unsustainable considering the increasing numbers of cases and the fact that a cure is not forthcoming.
...

http://observer.ug/lifestyle/55871-coming-face-to-face-with-nodding-disease.html

[Emily]

The article Pathfinder posted above says:

But since most of the affected children are teenage girls, this exposes them to rapists. ?Defilers watch from a distance and when parents leave home, they pounce on these helpless souls and shatter their only remaining source of pride ? their virginity,? Kanuela says. Many have been defiled and infected with HIV/Aids. In 2014, then Kitgum woman MP Beatrice Anywar said at least 50 girls with nodding syndrome had been raped and 35 impregnated. Kanuela says this is still the case. In most cases, the perpetrators are never found since many of these children are too sick to remember their tormentors. Even when they are caught, the damage they leave is life-long.

The research that ties B6 deficiency combined with genetics and environmental factors to this disease is strong enough and the illness devastating enough that including multiple vitamins with aid food should be considered to prevent further illnesses. I think the article below indicates that only the amount in the average daily multiple could be adequate.

http://www.panafrican-med-journal.com/content/article/24/123/full/

Reduced plasma concentrations of vitamin B6 and increased plasma concentrations of the neurotoxin 3-hydroxykynurenine are associated with nodding syndrome: a case control study in Gulu and Amuru districts, Northern Uganda