Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the treatment of second stage gambiense human African trypanosomiasis

Figures & data

Table 1 Centers reporting NECT pharmacovigilance data

Country	Treatment center	Cases treated with NECT	Patients with AE
Central African Republic (CAR)	Hôpital Sous-préfectoral Batangafo	234 (13.5%)	152 (14.5%)
	Hôpital Maitikoulou	30 (1.7%)	21 (2.0%)
Chad	Hôpital Moissala	23 (1.3%)	3 (0.3%)
	Centre de Santé Bodo Est	131 (7.5%)	76 (7.3%)
Democratic Republic of Congo (DRC)	Hôpital, Roi Baudouin, Kinshasa	60 (3.6%)	31 (3.0%)
	HGR (Hôpital General de Reference) de Doruma	378 (21.8%)	236 (22.6%)
	HGR de Dingila	538 (31.0%)	450 (43.1%)
	CDTC (Centre de Dépistage, Traitement et Contrôle) de Katanda	20 (1.1%)	2 (0.2%)
	CRT (Centre de Référence et de Traitement) de Dipumba	40 (2.3%)	2 (0.2%)
Equatorial Guinea South Sudan	Hospital Regional de Bata	12 (0.7%)	8 (0.8%)
	Juba Teaching Hospital	7 (0.4%)	1 (0.1%)
	Yei Civil Hospital	72 (4.1%)	23 (2.2%)
	Lui Hospital	38 (2.2%)	10 (1.0%)
	Nimule Hospital	14 (0.8%)	6 (0.6%)
	Yambio Hospital	27 (1.6%)	2 (0.2%)
Uganda	Adjumani District Hospital	13 (0.7%)	3 (0.3%)
	Omugo Health Center	47 (2.7%)	11 (1.0%)
	Yumbe District Hospital	12 (0.7%)	1 (0.1%)
	Moyo District Hospital	23 (1.3%)	0 (0.0%)
Cote d’Ivoire	PRCT Daloa	3 (0.2%)	1 (0.1%)
Congo	Hôpital Ngabe	3 (0.2%)	2 (0.2%)
Guinea	Hypnoserie Dubreka	10 (0.6%)	2 (0.2%)
Total		1735	1043

Abbreviations: AE, adverse events; NECT, nifurtimox-eflornithine combination therapy.

Table 2 Total adverse events reported (according to CTCAE classification)

AE	Total		Adults (≥15 years)		Children (<15 years)
	Total	Related to NECT	Total	Related to NECT	Total	Related to NECT
Gastrointestinal disorders	1214	1138	1017	995	196	183
Vomiting	429	413	339	327	90	86
Gastrointestinal pain	242	239	228	226	14	13
Nausea	214	212	179	178	35	34
Abdominal pain	201	171	158	134	42	37
Diarrhea (including dysentery)	100	82	88	71	12	11
Others	28	21	25	19	3	2
Nervous system disorders	522	474	478	439	40	32
Headache	308	271	281	249	25	21
Seizure	106	102	100	97	6	5
Tremor	68	63	65	61	3	2
Others	40	38	32	32	6	4
General disorders	257	212	220	189	34	21
Fatigue, asthenia, malaise	121	121	115	115	5	5
Fever	94	53	69	41	25	12
Others	42	38	36	33	4	4
Musculoskeletal and connective tissue disorders	245	205	232	199	12	6
Back pain	100	81	91	78	9	3
Neck pain	77	68	75	66	2	2
Others	68	56	66	55	1	1
Psychiatric disorders	242	233	228	222	10	9
Insomnia	102	101	101	100	1	1
Agitation, anxiety	48	42	39	35	7	6
Others	92	90	88	87	2	2
Ear and labyrinth disorders	201	199	195	195	6	4
Vertigo/dizziness	190	190	186	186	4	4
Others	11	9	9	9	2	0
Metabolism and nutrition disorders	166	165	140	139	26	26
Anorexia	164	163	138	137	26	26
Others	2	2	2	2	0	0
Skin and subcutaneous tissue disorders	59	50	53	45	6	5
Pruritus	50	44	46	41	4	3
Others	9	6	7	4	2	2
Vascular disorders	55	42	47	37	8	5
Respiratory, thoracic and mediastinal disorders	31	23	21	15	9	7
Infections and infestations	19	10	15	8	4	2
Eye disorders	19	17	18	16	1	1
Renal and urinary disorders	14	12	13	12	0	0
Cardiac disorders	12	12	12	12	0	0
Blood and lymphatic system disorders	4	2	3	2	1	0
Total	3060	2794	2692	2485	353	301

Abbreviations: CTCAE, common toxicity criteria for adverse events; NECT, nifurtimox-eflornithine combination therapy.

Table 3 Patients with serious adverse events reported

No	Event	Considered related to NECT	Death	Compatible with reactive encephalopathy?
1	Depressed level of consciousness with fever and death	No	Yes	No
2	Coma with seizures and death	Yes	Yes	Yes
3	Coma with seizures and fever	Yes	No	Yes
4	Coma with hypotension, seizures, fever, and death	Yes	Yes	Yes
5	Ataxia and urinary retention	Yes	No	No
6	Psychotic reaction	Yes	No	No
7	High fever and death	No	Yes	No
8	High fever and death	Yes	Yes	Yes
9	Agitation, abnormal behavior, fever, and encephalopathy	Yes	No	Yes
10	Severe anemia and death	No	Yes	No
11	Fever and seizures	Yes	No	Yes
12	Fever, seizures, coma, and death	Yes	Yes	Yes
13	Repeated seizures	Yes	No	Yes
14	Severe dyspnea	Yes	No	No
15	Seizure and encephalopathy	Yes	No	Yes
16	Paralysis	Yes	No	No
17	Seizure, confusion, paralysis	Yes	No	Yes
18	Acute abdomen and death	No	Yes	No
19	Confusion, coma, and death	Yes	Yes	Yes

Abbreviation: NECT, nifurtimox-eflornithine combination therapy.

Table 4 Distribution of cases treated and presenting AE according to age group

Age	Cases treated	Patients with AE
0–4 years	40 (2.3%)	26 (2.5%)
5–14 years	222 (12.8%)	129 (12.4%)
>14 years	1452 (83.7%)	876 (84.0%)
NA	21 (1.2%)	12 (1.1%)
Total	1735	1043

Abbreviations: AE, adverse events; NA, not available.

Table 5 Comparison of eflornithine monotherapy treatment (in the NECT clinical trial,^7,8 and during routine use in the Ibba MSF treatment Centre, South Sudan),²⁰ and NECT (in the NECT clinical trial^7,8 and in routine use as monitored by WHO)

	Eflornithine				NECT
	NECT clinical trial		Control program Ibba (S. Sudan)		NECT clinical trial		Routine use PV system
	n	%	n	%	n	%	n	%
Cases treated (n)	143		1055		143		1735
Cases with at least one AE	134	93.7	962	91.2	134	93.7	1043	60.1
Cases with major clinical AE	33	23.1	138	13.1	18	12.6	189	10.9
Cases with SAE	6	4.2			1	0.7	19	1.1
Cases requiring treatment interruption	9	6.3	109	10.3			45	2.6
Deaths during treatment	3	2.1	16	1.5	1	0.7	9	0.5

Abbreviations: AE, adverse event; MSF, Médecins Sans Frontières; NECT, nifurtimox-eflornithine combination therapy; SAE, serious adverse event; WHO, World Health Organization.

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