Nodding disease

Last updated
Nodding disease
Other namesNodding syndrome
Sudan districts affected by nodding disease.svg
Map of counties of South Sudan affected by nodding disease in 2011. Several of these are in the Central Equatoria state, in the south of the country near the border with Uganda; Juba on the White Nile is the nation's capital. The red district was already affected in 2001, in yellow districts the disease was prevalent as of 2011 and in green districts there are only sporadic reports. [1]
Specialty Infectious disease

Nodding disease, also known as nodding syndrome, is a mentally and physically disabling disease that affects children aged 3 and above, continuing into adulthood. [2] It was first described in 1962 in secluded mountainous regions of Tanzania, with sporadic outbreaks in the decades since in South Sudan, Uganda, and again in Sudan with its largest outbreak from 2016 to present. [2] [3] [4] [5] Since 2019 cases have been identified in the Democratic Republic of the Congo, Central African Republic and Cameroon.

Contents

Its cause is unknown, and no cure yet exists. [2]

Signs and symptoms

Children affected by nodding disease experience a complete and permanent stunting of growth. The growth of the brain is also stunted, leading to intellectual disability. The disease is named for the characteristic, pathological nodding seizure, which often begins with the sight of food or dropping temperatures. [2] [6] These seizures are brief and halt after the children stop eating or when they feel warm again. Seizures in nodding disease span a wide range of severity. Neurotoxicologist Peter Spencer, who has investigated the disease, has stated that upon presentation with food, "one or two [children] will start nodding very rapidly in a continuous, pendulous nod. A nearby child may suddenly go into a tonic–clonic seizure, while others will freeze." [7] Severe seizures can cause the child to collapse, causing injury. [8] Sub-clinical seizures have been identified in electroencephalograms, and MRI scans have shown brain atrophy and damage to the hippocampus and glia cells. [4]

It has been found that no seizures occur when affected individuals are given an unfamiliar or non-traditional food, such as chocolate. [6] [8] [9]

Causes

As of 2024 the cause of the disease was not known, [2] but a link has been found between nodding syndrome, infestation by the parasitic worm Onchocerca volvulus prevalent in all outbreak areas, and exposure to black-fly bites which transmit it. [10] [2] A possible explanation involves the formation of antibodies against parasite antigen that are cross-reactive to leiomodin-1 in the central nervous system. [11] O. volvulus, a nematode, is carried by the black fly and causes river blindness. In 2004, most children with nodding disease lived close to the Yei River, a hotbed for river blindness, and 93.7% of those with nodding disease were found to harbour the parasite — a far higher percentage than in children without the disease. [12] A link between river blindness and normal cases of epilepsy, [13] as well as retarded growth, [14] had been proposed previously, although the evidence for this link is inconclusive. [15] Of the connection between the worm and the disease, Scott Dowell, the lead investigator into the syndrome for the US Centers for Disease Control and Prevention (CDC), stated: "We know that [Onchocerca volvulus] is involved in some way, but it is a little puzzling because [the worm] is fairly common in areas that do not have nodding disease". [10] Andrea Winkler, the first author of a 2008 Tanzanian study, has said of the connection: "We could not establish any hint that Onchocerca volvulus is actually going into the brain, but what we cannot exclude is that there is an autoimmune mechanism going on." [4] In the most severely affected region of Uganda, infection with microfilariae in epileptic or nodding children ranged from 70% to 100%. [16]

In 2011 the CDC was investigating a possible connection with wartime chemical exposure, and whether a deficiency in vitamin B6 (pyridoxine) could be a cause, noting the seizures of pyridoxine-dependent epilepsy and this common deficiency in those with the disease. [4] Older theories include a 2002 toxicology report that postulated a connection with tainted monkey meat, as well as the eating of agricultural seeds provided by relief agencies that were covered in toxic chemicals. [6]

Diagnosis

Diagnosis is not very advanced and is based on the telltale nodding seizures of the patients. When stunted growth and mental disability are also present, probability of nodding syndrome is high. In the future, neurological scans may also be used in diagnosis. [17]

Management

As of 2024 no cure was known for the disease, [2] so treatment has been directed at symptoms, and has included the use of anticonvulsants used to treat epilepsy such as sodium valproate [10] and phenobarbitol. Anti-malaria drugs have also been administered, to unknown effect. [7] Nutritional deficiencies may also be present.

Prognosis

Nodding syndrome is debilitating both physically and mentally. In 2004, Peter Spencer stated: "It is, by all reports, a progressive disorder and a fatal disorder, perhaps with a duration of about three years or more." [7] Without epilepsy drugs, the condition worsens; seizures can cause accidents [9] and even death. Long-term effects include brain damage, stunted growth and mental impairment. [2] A few children are said to have recovered from the disease, but many have died. [6]

Epidemiology

While the majority of occurrences of the disease known as "nodding syndrome" have been relatively recent, it appears that the condition was first documented in 1962 in southern Tanzania. [4] More recently, nodding syndrome had become most prevalent in South Sudan, where in 2003 approximately 300 cases were found in Mundri alone. By 2009, it had spread across the border to Uganda's Kitgum district, [3] and the Ugandan ministry of health declared that more than 2000 children had the disease. [4] As of the end of 2011, outbreaks were concentrated in Kitgum, Pader and Gulu. More than 1000 cases were diagnosed in the last half of that year. [10]

There were further outbreaks in early 2012, in South Sudan, Uganda, and Tanzania. [18] In the five years to 2024 cases have been identified in the Democratic Republic of the Congo, Central African Republic and Cameroon. [2]

The spread and manifestation of outbreaks may further be exacerbated due to the poor availability of health care in the region. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

<i>Loa loa</i> filariasis Medical condition

Loa loa filariasis, (Loiasis) is a skin and eye disease caused by the nematode worm Loa loa. Humans contract this disease through the bite of a deer fly or mango fly, the vectors for Loa loa. The adult Loa loa filarial worm can reach from three to seven centimetres long and migrates throughout the subcutaneous tissues of humans, occasionally crossing into subconjunctival tissues of the eye where it can be easily observed. Loa loa does not normally affect vision but can be painful when moving about the eyeball or across the bridge of the nose. Loiasis can cause red itchy swellings below the skin called "Calabar swellings". The disease is treated with the drug diethylcarbamazine (DEC), and when appropriate, surgical methods may be employed to remove adult worms from the conjunctiva. Loiasis belongs to the group of neglected tropical diseases, and there is a call for it to be included in the high priority listing.

<i>Loa loa</i> Species of roundworm

Loa loa is a filarial (arthropod-borne) nematode (roundworm) that causes Loa loa filariasis. Loa loa actually means "worm worm", but is commonly known as the "eye worm", as it localizes to the conjunctiva of the eye. Loa loa is commonly found in Africa. It mainly inhabits rain forests in West Africa and has native origins in Ethiopia. The disease caused by Loa loa is called loiasis and is one of the neglected tropical diseases.

<span class="mw-page-title-main">Onchocerciasis</span> Human helminthiasis (infection by parasite)

Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm Onchocerca volvulus. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindness due to infection, after trachoma.

<span class="mw-page-title-main">Filariasis</span> Parasitic disease caused by a family of nematode worms

Filariasis, is a filarial infection caused by parasitic nematodes (roundworms) spread by different vectors. They are included in the list of neglected tropical diseases.

<span class="mw-page-title-main">Helminthiasis</span> Any macroparasitic disease caused by helminths

Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. They often live in the gastrointestinal tract of their hosts, but they may also burrow into other organs, where they induce physiological damage.

<i>Onchocerca volvulus</i> Nematode

Onchocerca volvulus is a filarial (arthropod-borne) nematode (roundworm) that causes onchocerciasis, and is the second-leading cause of blindness due to infection worldwide after trachoma. It is one of the 20 neglected tropical diseases listed by the World Health Organization, with elimination from certain countries expected by 2025.

<span class="mw-page-title-main">Health in Uganda</span> Overview of health in Uganda

According to the recently conducted national survey in 2024, Uganda's population stands at 45.9 million. Health status is measured by some of the key indicators such as life expectancy at birth, child mortality rate, neonatal mortality rate and infant mortality rate, maternal mortality ratio, nutrition status and the global burden of disease. The life expectancy of Uganda has increased from 39.3 in 1950 to 62.7years in 2021. This is lower below the world average which is at 71.0 years. The fertility rate of Ugandan women slightly increased from an average of 6.89 babies per woman in the 1950s to about 7.12 in the 1970s before declining to an estimate 4.3 babies in 2019. This figure is higher than the world average of 2 and most world regions including South East Asia, Middle East and North Africa, Europe and Central Asia and America. The under-5-mortality-rate for Uganda has decreased from 191 deaths per 1000 live births in 1970 to 41 deaths per 1000 live births in 2022.

Brian Oliver Lyndhurst Duke CBE M.D., ScD was an expert in tropical diseases who extensively studied River Blindness and other parasitic diseases. His work helped to develop an anti parasitic drug to combat them.

In population ecology, density-dependent processes occur when population growth rates are regulated by the density of a population. This article will focus on density dependence in the context of macroparasite life cycles.

Mansonelliasis is the condition of infection by the nematode Mansonella. The disease exists in Africa and tropical Americas, spread by biting midges or blackflies. It is usually asymptomatic.

<span class="mw-page-title-main">Eradication of infectious diseases</span> Elimination of a disease from all hosts

The eradication of infectious diseases is the reduction of the prevalence of an infectious disease in the global host population to zero.

Mansonella streptocerca is a filarial (arthropod-borne) nematode (roundworm) causing the disease streptocerciasis. It is a common parasite in the skin of humans in the rain forests of Africa, where it is thought to be a parasite of non-human primates, as well.

<span class="mw-page-title-main">Pyridoxine-dependent epilepsy</span> Medical condition

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period. The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954. More recently, pathogenic variants within the ALDH7A1 gene have been identified to cause PDE.

Avindra "Avi" Nath, is a physician-scientist who specializes in neuroimmunology. Nath is a senior investigator, and intramural clinical director of the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) in the United States. At NINDS, Nath also leads the Section of Infections of the Nervous System and plans to institute a translational research center. He previously served in several research and administrative positions at the Johns Hopkins Hospital and the Johns Hopkins University School of Medicine.

Onchocerca lupi is a nematode that causes ocular onchocerciasis, an eye disease, in canines and felines. The parasite was first described in 1967 in a wolf from Georgia. The other Onchocerca spp., O. volvulus, is a human parasite that causes ocular onchocerciasis in human and affects 37 million people globally.

Richard Iwa Idro is a Ugandan pediatric neurologist, researcher and academic, who serves as an associate professor in the Department of Pediatrics and Child Health at Makerere University College of Health Sciences.

The Raga River is a river of South Sudan, a right tributary of the Boro River.

<span class="mw-page-title-main">2022–2023 Uganda Ebola outbreak</span> Disease outbreak in East Africa

The 2022–2023 Uganda Ebola outbreak was an outbreak of the Sudan ebolavirus, which causes Ebola, from 20 September 2022 until 10 January 2023 in the Western and Central Regions of Uganda. Over 160 people were infected, including 77 people who died. It was Uganda's fifth outbreak with Sudan ebolavirus. The Ugandan Ministry of Health declared the outbreak on 20 September 2022. As of 25 October 2022, there were confirmed cases in the Mubende, Kyegegwa, Kassanda, Kagadi, Bunyanga, Kampala and Wakiso districts. As of 24 October 2022, there were a total of 90 confirmed or probable cases and 44 deaths. On 12 October, the first recorded death in the capital of Kampala occurred; 12 days later on 24 October, there had been a total of 14 infections in the capital in the last two days. On 11 January 2023 after 42 days without new cases the outbreak was declared over.

<span class="mw-page-title-main">Robert Colebunders</span> Belgian infectious disease physician

Robert Colebunders is a Belgian clinician and researcher specialising in infectious diseases and epidemiology, particularly in the study and management of emerging pathogens and tropical diseases including Ebola, AIDS, tuberculosis and onchocerciasis. Colebunders investigated major outbreaks, such as the Ebola and Marburg virus epidemics, and has contributed to research on COVID-19 and monkeypox. His current work focuses on onchocerciasis-associated epilepsy (OAE), a condition prevalent in regions where river blindness (onchocerciasis) is endemic. He is professor emeritus at the Institute of Tropical Medicine Antwerp (ITM), Belgium, and continues to lead international research efforts on infectious diseases at the Global Health Institute.

References

  1. ↑ Meredith Wadman (13 July 2011). "Box: A growing threat". Nature . Retrieved 11 July 2011.
  2. 1 2 3 4 5 6 7 8 9 Miettaux, Florence (25 March 2024). "The fight to cure South Sudan's mysterious neurological disorder". The Guardian.
  3. 1 2 "Nodding disease or 'river epilepsy'?". IRIN Africa. 10 August 2009. Archived from the original on 17 February 2019.
  4. 1 2 3 4 5 6 Wadman, Meredith (13 July 2011). "African outbreak stumps experts". Nature. Retrieved 25 December 2011.
  5. ↑ McKenzie, David (19 March 2012). "Mysterious nodding disease debilitates children". CNN.
  6. 1 2 3 4 'Nodding disease' hits Sudan Andrew Harding BBC News 23 September 2003
  7. 1 2 3 4 Ross, Emma (3 February 2004). "Sudan A Hotbed Of Exotic Diseases". CBS News. Rumbek, Sudan. Archived from the original on February 18, 2004. Retrieved 25 December 2011.
  8. 1 2 Ross, Emma (January 28, 2004). "Bizarre Illness Terrifies Sudanese". CBS News. Kacnguan, Sudan. Associated Press. Archived from the original on October 9, 2007. Retrieved October 19, 2007.
  9. 1 2 "World Health Organization joins other partners to support Nodding Disease investigations in Southern Sudan". World Health Organisation. Archived from the original on March 25, 2012. Retrieved 25 December 2011.
  10. 1 2 3 4 Abraham, Curtis (23 December 2011). "Mysterious nodding syndrome spreading through Uganda". New Scientist. Retrieved 25 December 2011.
  11. ↑ Johnson, Tory P.; Tyagi, Richa; Lee, Paul R.; Lee, Myoung-Hwa; Johnson, Kory R.; Kowalak, Jeffrey; Elkahloun, Abdel; Medynets, Marie; Hategan, Alina (2017-02-15). "Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus". Science Translational Medicine. 9 (377): eaaf6953. doi:10.1126/scitranslmed.aaf6953. ISSN   1946-6234. PMC   5434766 . PMID   28202777.
  12. ↑ When Nodding Means Dying: A baffling new epidemic is sweeping Sudan. Lekshmi Santhosh The Yale Journal of Public Health Vol. 1, No. 1, 2004. Accessed 25 December 2011
  13. ↑ Druet-Cabanac M, Boussinesq M, Dongmo L, Farnarier G, Bouteille B, Preux PM (2004). "Review of epidemiological studies searching for a relationship between onchocerciasis and epilepsy". Neuroepidemiology. 23 (3): 144–9. doi:10.1159/000075958. PMID   15084784. S2CID   10903855.
  14. ↑ Ovuga E, Kipp W, Mungherera M, Kasoro S (1992). "Epilepsy and retarded growth in a hyperendemic focus of onchocerciasis in rural western Uganda". East African Medical Journal. 69 (10): 554–6. PMID   1473507.
  15. ↑ Marin B, Boussinesq M, Druet-Cabanac M, Kamgno J, Bouteille B, Preux PM (2006). "Onchocerciasis-related epilepsy? Prospects at a time of uncertainty". Trends Parasitol. 22 (1): 17–20. doi:10.1016/j.pt.2005.11.006. PMID   16307906.
  16. ↑ Dan Michael Komakech (2011-11-07). "Nodding disease community dialogue meeting held in Pader district". Acholi Times.
  17. ↑ "CDC - Global Health - Nodding Syndrome". www.cdc.gov. Retrieved 2017-03-29.
  18. ↑ "East African Mystery Disease: Nodding Syndrome". Daily Kos. March 14, 2012. Retrieved March 14, 2012.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.