Caregiver Training to Prevent Konzo Disease in Children in Democratic Republic of Congo

Caregiver Early Child Development Training for Preventing Konzo From Toxic Cassava in the Democratic Republic of Congo

The proposed research will adapt the caregiver training and child neurodevelopmental assessment capacity that the PI previously built in Uganda beginning in 2008, to a community-based intervention model for the prevention of konzo in the Democratic Republic of Congo.

Early childhood (1 through 4 yrs) is a period of dramatic developmental change that can be seriously compromised by exposure to toxic cyanogenic cassava (konzo disease), with potentially great impact throughout central and western sub-Sahara Africa in regions dependent on this food staple. In the face of ongoing economic instability and nutritional, medical and educational deprivation affecting konzo at-risk communities in the Democratic Republic of Congo, no programs exist for sustaining a favorable developmental milieu for these children. By establishing the viability of caregiver training interventions to enhance functionality among caregivers and improve caregiving quality while preventing konzo, the present R21 proposal can benefit tens of millions of children at-risk neurodevelopmentally; not only from poorly processed cyanogenic cassava, but also from a myriad of other non-infectious and infectious diseases.

Wetting method (WTM)+ Mediational Intervention for Sensitizing Caregivers (MISC) bi-weekly for 12 months.

The wetting method is an evidence-based, simple process to remove cyanogens from cassava flour. It involves teaching women to add water to cassava flour and allow it to stand for 2 h in the sun or 5 h in the shade for the hydrogen cyanide gas to escape. Colorfully illustrated and durable laminated posters depicting the WTM will be distributed to participating households. Women will receive this training bi-weekly for 12 months

The study team will use MISC to train DRC mothers in practical day-to-day activities with their children to enhance 5 key mediational processes: 1) focusing (getting the child's attention and engaging directing them to learning experiences); 2) exciting (communicating excitement, appreciation, and affection with the learning experience); 3) expanding (making the child aware of how the learning experience transcends the present situation and can include past and future issues beyond the immediate need of the moment); 4) encouraging (emotional support to foster the child's sense of security and competence); and 5) regulating (helping to direct the child's behavior in constructive ways with a goal towards self-regulation).

The MSEL is a comprehensive test assessing specific developmental domains: visual reception, gross motor skills, fine motor skills, receptive language, and expressive language. Each sub-scale produces a raw and a standardized score. A composite score derived from standardized t-scores of the four domains (excluding gross motor) provides a measure of g, the general measure of fluid intelligence thought to underlie general cognitive ability.

Home-based video recordings of mother-child interactions while feeding, bathing and playing will be scored by a trained observer using an ad hoc rubric covering areas of focusing, exciting, expanding, encouraging, and regulating caregiver/child interactions consistent with the MISC training

Technicians will collect samples of urine and cassava flour on the same day as child assessments, so that they are contiguous with level of cyanide exposure from current poorly processed cassava. We will measure thiocyanite levels (micromol/l) in urine using the SCN picrate kit D1 and B2 protocols. We will measure the cyanide-yielding capacity in household cassava flour, and thiocyanate (SCN, metabolite of cyanide) in urine

Composite measure designed to assess the quality and quantity of stimulation that the child is exposed to in their home environment. The Infant/Toddler version includes 45 yes/no items. A total HOME score was generated by summing the number of 'yes' responses; higher HOME scores indicate higher quality interactions.

Questionnaire consisting of two subscales: anxiety (10 items) and depression (15 items) symptoms to evaluate caregiver well-being. Caregivers indicate how frequently they experienced each symptom in the last two weeks on a scale of 0 (not at all) to 3 (a lot). Subscale scores will be calculated by averaging item responses.

12-item measure assessing degree of difficulty performing tasks women regularly do to care for themselves, their family, their community and their young child. Caregivers indicate how much difficulty they had completing each task, with responses ranging from 0 (no difficulty at all) to 4 (cannot complete). An impairment scale will be calculated by averaging item responses

Neurological evaluation to establish study eligibility with no symptoms of konzo disease. This neurological exam will also be used as a primary outcome for WTM adherence and low levels of cyanide exposure by quantifying the number and severity of each symptom using a rubric

The Durkin Ten Question Questionnaire (TQQ) screening inventory to assess number and severity of neurodisabilities. It is a parent report screening tool for developmental disabilities, that has been used in epidemiological studies, surveys and as a clinical screening tool. An average score is derived summing all responses

Inclusion Criteria: Kahemba district households with at least 1 child 4 years or younger Mother is the primary caregiver of child Exclusion Criteria: History of brain injury (infectious, traumatic, birth) in child Konzo disease in any family member of household Epilepsy in child Any neurodisability in child Caregiver is unable to participate in the year-long training Caregiver or child are presently enrolled in our parent R01 study

The study coordinator assigns a unique identification number to each research subject at entry into the study. The first page of the risk-factor questionnaire, which contains identifying information, names and addresses, is removed after data entry and stored at the field office in a locked file dedicated to this research study. The data files will include only study numbers, which are linked through a security system to a named file maintained for the purpose of informing individuals of information pertinent to their health. The name file is only accessible to the PI Professor Michael Boivin.

Tshala-Katumbay D, Mumba N, Okitundu L, Kazadi K, Banea M, Tylleskar T, Boivin M, Muyembe-Tamfum JJ. Cassava food toxins, konzo disease, and neurodegeneration in sub-Sahara Africans. Neurology. 2013 Mar 5;80(10):949-51. doi: 10.1212/WNL.0b013e3182840b81.

Boivin MJ, Okitundu D, Makila-Mabe B, Sombo MT, Mumba D, Sikorskii A, Mayambu B, Tshala-Katumbay D. Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis. Lancet Glob Health. 2017 Sep;5(9):e936-e947. doi: 10.1016/S2214-109X(17)30267-X.

Boivin MJ, Okitundu D, Makila-Mabe Bumoko G, Sombo MT, Mumba D, Tylleskar T, Page CF, Tamfum Muyembe JJ, Tshala-Katumbay D. Neuropsychological effects of konzo: a neuromotor disease associated with poorly processed cassava. Pediatrics. 2013 Apr;131(4):e1231-9. doi: 10.1542/peds.2012-3011. Epub 2013 Mar 25.

Kashala-Abotnes E, Sombo MT, Okitundu DL, Kunyu M, Bumoko Makila-Mabe G, Tylleskar T, Sikorskii A, Banea JP, Mumba Ngoyi D, Tshala-Katumbay D, Boivin MJ. Dietary cyanogen exposure and early child neurodevelopment: An observational study from the Democratic Republic of Congo. PLoS One. 2018 Apr 17;13(4):e0193261. doi: 10.1371/journal.pone.0193261. eCollection 2018.