Epidemiology of Diphtheria and Predictors of Outcome in Nigeria: A Single-Center  Study from July 2023 to April 2024

doi:10.21203/rs.3.rs-4973472/v1

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Epidemiology of Diphtheria and Predictors of Outcome in Nigeria: A Single-Center Study from July 2023 to April 2024

https://doi.org/10.21203/rs.3.rs-4973472/v1

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Background:

Despite recurrent outbreaks of diphtheria in Nigeria, there is a lack of in-depth analysis of hospitalization outcomes. Herein, we describe the sociodemographic, clinical, and laboratory features that were associated with hospitalization outcomes (defined as death or discharge) during the recent diphtheria outbreak in Nigeria.

Methods

This prospective observational study included 246 diphtheria cases managed in a dedicated isolation ward of a health facility in northwestern Nigeria from July 1, 2023, to April 30, 2024. We adopted the case definition for diphtheria from the Nigeria Center for Disease Control and Prevention (NCDC).

Results

The median age (interquartile range) was 7.00 (4–10) years, and half of the patients were aged 5–10 years (49.6%). The common clinical features were fever (95.9%), sore throat (91.9%), painful swallowing (90.7%), pseudomembrane (93.1%), and cervical-submandibular lymphadenopathy (91.5%). Most children were unvaccinated (158; 64.2%), and 199 (80.9%) received diphtheria antitoxin. Of the 246 cases of diphtheria, 58 in-hospital deaths occurred, with a crude mortality rate of 23.6%. After adjusting for confounders, the variables that predicted hospitalization deaths were neck swelling with an adjusted odds ratio (AOR) of 9.8 (95% CI 1.686–56.469), abnormal respiratory findings (AOR, 149.987 [95% CI, 15.600–1442.023] ), hypoxemia (AOR, 37.785 [95% CI, 4.255–331.962] ), and elevated serum creatinine above 1.5 mg/dL (AOR 107.783, 95% CI, 7.944–1462.376).

Conclusions

Diphtheria, a re-emerging disease, constitutes a significant burden in Nigeria, especially among children. Neck swelling, hypoxemia, abnormal respiratory findings and impaired renal function are predictive of hospitalized death.

Diphtheria

clinical features

laboratory findings

Outcomes

Nigeria

Diphtheria is a potentially life-threatening infectious disease caused by the bacterium Corynebacterium diphtheriae [1]. The re-emergence of the disease continues to cause significant morbidity and mortality, especially in low- and middle-income countries, including Nigeria [2–4]. Despite the availability of effective vaccines and antibiotics, it has remained a significant public health concern in Nigeria, with recurrent outbreaks [4]. The vulnerability and spread of diphtheria in the country are due to various factors, including incomplete or lack of immunization, low levels of education, poor knowledge of the disease, poverty, misconceptions, and certain religious beliefs [5][6]. Studies conducted in India and Nigeria found that 57.0% and 45.8% of children hospitalized with diphtheria, respectively, were completely immunized according to the national immunization schedule [2, 3]. The findings also suggests that vaccinated children can develop severe disease and highlights the importance of maintaining high vaccination coverage to prevent outbreaks.

Diphtheria, especially in severe cases, requires hospitalization due to potentially serious complications such as respiratory failure, cardiac arrest, and even death if left untreated [1, 7]. Hospitalization is also required for the administration of diphtheria antitoxin. Previous studies in Nigeria show a complete lack of diphtheria antitoxin in the country, which partly accounted for the high mortality recorded in the past [8]. Besides the availability of antitoxin, there are other associated factors, including socio-demographics, the severity of the disease, and clinical and laboratory features, that may influence the hospitalization and outcomes of cases of diphtheria [9][10]. Understanding these factors associated with outcomes in hospitalized diphtheria cases is critical for developing effective strategies to improve patient care and reduce mortality rates. Therefore, this study aimed to investigate the factors (socio-demographics, clinical features, and laboratory features) associated with outcomes in children hospitalized with diphtheria at a single Nigerian tertiary hospital. We reviewed 246 cases of prospectively gathered data on diphtheria managed during the recent outbreak in Nigeria from July 2023 to April 2024 to identify the factors influencing the outcomes of hospitalization (discharge or death). By understanding these factors, health care providers can develop targeted interventions to improve patient outcomes and reduce mortality rates in diphtheria.

Study design and setting:

This prospective observational study involved cases of diphtheria managed from July 1, 2023, to April 30, 2024, at a tertiary health facility in northwestern Nigeria. The hospital is the only tertiary health facility in the state with a dedicated 15-bed isolation ward for highly infectious diseases. The facility receives and manage diphtheria cases in the state, with an estimated population of 9.3 million (2024), and members of the infectious disease unit included consultants, resident doctors, nurses, and attendants.

Study population

This study included all cases of diphtheria (pediatrics and adults) that presented and were admitted to the isolation ward of the hospital during the study period (July 1st 2023 to April 30th 2024). We excluded patients with other forms of diagnoses during the study period.

Sample size

The minimum sample size was estimated using an online calculator (http://www.raosoft.com/samplesize.html). Using an incidence of 3.1% of diphtheria cases reported earlier at the study site, we obtained a minimum sample size of 183 at a 95% confidence level and 2.5% margin of error [3] However, all cases (246) of diphtheria managed in the 10 months were included in the study.

Definition of terms

The case definition for diphtheria was adopted from the Nigeria Centre for Disease Control and Prevention (NCDC) [11] as follows: ‘Suspected case’ was defined as any patient with features of upper respiratory tract infection characterized by pharyngitis, nasopharyngitis, tonsillitis, laryngitis, and adherent pseudo-membrane of the pharynx, tonsils, larynx, and/or nose. Laboratory-confirmed case was defined as any case with confirmed Corynebacterium spp. toxin production by polymerase chain reaction, regardless of symptoms. The Nigeria National Reference Laboratory, situated at the NCDC Headquarters in Abuja, Nigeria, analyzed the samples.

Study outcomes

The primary outcomes were factors (socio-demographics, clinical, and laboratory features) that were associated with hospitalization outcomes (defined as death or discharge). The secondary outcomes included a description of the epidemiology (demographics) and complications associated with diphtheria.

Data collection

At the onset of the outbreak, a register (an Excel spreadsheet) was opened at the isolation center to capture the following variables at the point of admission: age, sex, address, symptoms, signs, complications, laboratory parameters (full blood counts, electrolytes, serum urea and creatinine and throat swab for pathogen identification), treatments received, including antitoxins, and hospitalization outcomes (defined as death or discharge).The spreadsheet was updated regularly and at the time of discharge.

Data analysis

We cleaned the data and exported to SPSS version 29 for analysis. The age was summarized by the median with an interquartile range (IQR). The discrete variables, sex, clinical and laboratory features were summarized with percentages and frequency tables and compared with chi-square, while continuous variables (not normally distributed) were compared using the Mann-Whitney U test. Variables that were significant (p value less than 0.05) on two-by-two tables were entered into a binary logistic regression table to identify factors associated with hospitalization outcomes (death), with death as the dependent variable. The results of the binary logistic regression were presented as adjusted odds ratios with 95% confidence intervals. For all levels of statistical significance, we set the p-value at less than 0.05.

Ethical consideration and approval.

The Federal Teaching Hospital Katsina Human Research Ethical Review Committee approved this study (FTHKTNHREC.REG.24/06/22C/173). This study was conducted in conformity with the declaration of Helsinki. We obtained informed consent from the adult participants and the caregivers/parents of the recruited children. We anonymously extracted the data from the spreadsheet and de-identified them before analysis. All the data were stored on a password-secured computer with absolute confidentiality.

Socio-demographic characteristics of the study subjects

This study included a total of 246 patients (pediatrics and adults) with a median age (IQR) of 7.0 (4–10) years, a minimum age of 11 months, and a maximum age of 36 years. Approximately half of the patients were children aged 5–10 years (49.6%) (Table 1). Overall, there were more females (138; 56.1%) and a higher median age (IQR) of 8.00 (4.00–8.00), p = 0.044 (Table 1). In addition, most patients were from the lower and middle socioeconomic classes (219; 89.0%).

Table 1

Socio-demographic characteristics of the patients
Variable	Total n = 246 (%)	Male n = 108 (%)	Female n = 138 (%)	p-value
Age (years)
0–1	3 (1.2)	0	3 (2.2)	0.036*
> 1 to < 5	63 (25.6)	30 (27.8)	33 (23.9)
5 to 10	122 (49.6)	54 (50.0)	68 (49.3)
11 to 15	49 (19.9)	24 (22.2)	25 (18.1)
> 15	9 (3.7)	0	9 (6.5)
Median (IQR)	7.00 (4.00–10.00)	6.00 (4.00–10.00)	8.00 (4.00–8.00)	0.044**
SEC
Upper	27 (11.0)	9 (8.3)	18 (13.0)	0.298***
Middle	87 (35.4)	43 (39.8)	44 (31.9)
Lower	132 (53.6)	56 (51.9)	76 (55.1)
Fischer Exact test; Mann-Whitney U; **Chi-square; IQR-Interquartile range; SEC-Socio-economic class.

Clinical and Laboratory features of the study population

The age groups and sex were comparable between those who survived and those who did not. The most common symptoms were fever (95.9%), sore throat (91.9%), and painful swallowing (90.7%). Symptoms at presentation associated with hospitalization outcomes included inability to swallow, drooling of saliva, cough, difficulty breathing, nasal discharge, nasal blockade, voice changes, and nasal regurgitation (Table 2). The most common signs at presentation were pseudomembrane (93.1%) and cervical-submandibular lymphadenopathy (91.5%). Neck swelling, exudates, tonsillar enlargement, blood nasal discharge, third heart sounds, abnormal chest findings, and hypoxemia were associated with hospitalization outcomes (Table 2).

Table 2

Clinical features of the study patients (baseline)
Variable	Subgroup	Total n = 246 (%)	Survivor n (188; 76.4%)	Non-survivor n (58; 23.6%)	P value
Age (years)	< 5	66 (26.8)	47	19	0.318
	5 to 10	122 (49.6)	93	29
	> 10	58 (23.6)	48	10
Sex	Male	108 (43.9)	87	21	0.177
	Female	138 (56.1)	101	37
SEC	Upper	27 (11.0)	22	5	0.026
	Middle	87 (35.4)	74	13
	Lower	132 (53.6)	92	40
Symptoms	Fever	236 (95.9)	179	57	0.302
	Sore throat	226 (91.9)	173	53	0.876
	Painful swallowing	223 (90.7)	170	54	0.827
	Inability to swallow	162 (65.9)	111	51	< 0.001
	Drooling of Saliva	71 (28.9)	46	25	0.006
	Cough	46 (18.7)	25	21	< 0.001
	Breathing difficulty	58 (23.6)	20	38	< 0.001
	Nasal discharge	45 (18.3)	26	19	0.001
	Nasal blockade	24 (9.8)	11	13	< 0.001
	Voice changes	98 (39.8)	64	34	< 0.001
	Nasal regurgitation	19 (7.7)	10	9	0.011
Signs	Cerv-sub. Lymp.	225 (91.5)	171	54	0.609
	Neck swelling	131 (53.3)	84	47	< 0.001
	Pseudomembrane	229 (93.1)	172	57	0.075
	Exudates	31 (12.6)	26	5	0.296
	Tonsillar enlargement	107 (43.5)	75	32	0.040
	Bloody nasal discharge	22 (8.9)	9	13	< 0.001
	Added HS	24 (9.8)	11	13	< 0.001
	Abn. chest findings	43 (17.5)	9	34	< 0.001
	Temp ≥ 38.5	42 (17.1)	31	11	0.661
	Hypoxemia	38 (15.4)	7	31	< 0.001
Contact Hx	Yes	136 (55.3)	102	34	0.559
Immunization status	No vaccination	158 (64.2)	111	47	0.008
	Partially vaccinated	31 (12.6)	26	5
	Fully vaccinated	57 (23.2)	51	6
Antitoxin*	Yes	199 (80.9)	158	41	0.024
SEC-Socioeconomic class; Cer-sub lymph-Cervical-submandibular lymphadenopathy; HS-Heart sounds, Abn-Abnormal; Temp-Temperature, Hx-History. *Diphtheria antitoxin

Most children were unvaccinated (158; 64.2%), and vaccination status was related to hospitalization outcomes. Of the 246 patients managed during the study period, 199 (80.9%) received diphtheria antitoxin, which was associated with hospitalization outcomes (Table 2).

The laboratory findings at presentation associated with outcomes included white blood cell counts, lymphocytes, neutrophils, serum bicarbonate levels, serum sodium levels, serum potassium levels, and serum creatinine levels (Table 3).

Table 3

Laboratory features in the study patients (baseline)
Variable	Total n (%)	Survivor n (%)	Non-survivor n (%)	p-value
WBC (x 10⁹/L)
≤ 10	119 (48.4)	101	18	0.003
> 10	127 (51.6)	87	40
Lymphocyte (%)
≤ 40	136 (55.3)	96	40	0.017
> 40	110 (44.7)	92	18
Neutrophils (%)
≤ 60	141 (57.3)	116	25	0.012
> 60	105 (42.7)	72	33
PCV (%)
≤ 20	6 (2.4)	3	3	0.057
21–30	72 (29.3)	50	22
> 30	168 (68.3)	135	33
Platelets (x 10⁹/L)
< 100	32 (13.0)	21	11	0.296
100–400	180 (73.2)	141	39
> 400	34 (13.8)	26	8
Bicarbonate (mmol/L)
≤ 15	69 (28.0)	44	25	0.004
> 15	177 (72.0)	144	33
Sodium (mmol/L)
≥ 135	157 (63.8)	130	27	0.002
< 135	89 (36.2)	58	31
Potassium (mmol/L)
≤ 4.5	199 (80.9)	160	39	0.002
> 4.5	47 (19.1)	28	19
Serum Cr (mg/dL)
≤ 1.5	220 (89.4)	182	38	< 0.001
> 1.5	26 (10.6)	6	20
WBC-white blood count.

Factors that predicted in-hospitalization mortality

Of the 246 patients with diphtheria admitted during the study period, 58 in-hospital deaths occurred, with a crude mortality rate of 23.6%. After adjusting for confounders including age and sex, variables that predicted hospitalization deaths were the presence of neck swelling with an adjusted odd ratio (AOR) of 9.8 (95% CI 1.686 to 56.469), abnormal chest findings on physical examination at presentation with an AOR of 149.987 (95% CI 15.600 to 1442.023), the presence of hypoxemia (AOR 37.785, 95% CI 4.255 to 331.962), and elevated serum creatinine above 1.5 mg/dL (AOR 107.783, 95% CI 7.944 to 1462.376) (Table 4).

Table 4

Baseline variables that predicted mortality (in-hospital death)
Variable	Categories	n	β	Std error (β)	Adjusted OR	(95% CI)	P value
Age (years)	< 5	66			Ref
	5 to 10	122	1.264	0.875	3.539	0.636, 19.681	0.149
	> 10	58	1.562	1.021	4.770	0.645, 35.249	0.126
Sex	Female	138			Ref
Sex	Male	108	0.025	0.729	1.025	0.245, 4.281	0.973
SEC	Upper	27			Ref
	Middle	87	-0.757	1.543	0.469	0.023, 9.647	0.623
	Lower	132	0.800	1.392	2.226	0.145, 34.051	0.565
Inability to swallow	Yes#	162	0.550	0.946	1.734	0.272, 11.061	0.561
Drooling of Saliva	Yes#	71	-0.381	0.749	0.683	0.157, 2.964	0.611
Cough	Yes#	46	0-.134	0.941	0.874	0.138, 5.525	0.886
Difficulty in breathing	Yes#	58	-0.759	0.942	0.468	0.074, 2.964	0.420
Nasal discharge	Yes#	45	-0.689	1.000	0.502	0.071, 3.561	0.491
Nasal blockade	Yes#	24	0.059	1.204	1.060	0.100, 11,230	0.961
Voice changes	Yes#	98	0.289	0.770	1.336	0.295, 6.044	0.707
Nasal regurgitation	Yes#	19	1.178	0.808	2.883	0.287, 29.000	0.369
Immunization status	Fully vaccinated	57			Ref
	Partially vaccinated	31	0.039	0.839	1.040	0.201, 5.383	0.963
	No vaccination	158	0.393	1.296	1.481	0.117, 18.773	0.762
Neck swelling	Yes#	131	2.278	0.896	9.757	1.686, 56.469	0.011
Tonsillar enlargement	Yes#	107	1.823	0.814	6.190	1.255, 30.538	0.025
Bloody nasal discharge	Yes#	22	0.115	1.158	1.122	0.116, 10.851	0.921
Heart sounds	Added sounds**	24	0.449	0.921	1.567	0.258, 9.534	0.626
Chest	Abnormal findings**	43	5.011	1.155	149.987	15.600, 1442.023	< 0.001
Hypoxemia	Yes#	38	3.627	1.111	37.585	4.255, 331.962	0.001
WBC (x 10⁹/L)	≤ 10	119			Ref
WBC (x 10⁹/L)	> 10	127	0.368	0.757	1.446	0.328, 6.374	0.626
Lymphocyte (%)	≤ 40	136			Ref
Lymphocyte (%)	> 40	110	1.349	1.319	3.852	0.290, 51.074	0.307
Neutrophils (%)	≤ 60	141			Ref
Neutrophils (%)	> 60	105	1.860	1.291	6.426	0.512, 80.673	0.150
Bicarbonate	> 15	177			Ref
Bicarbonate	≤ 15	69	-1.066	0.877	0.344	0.700, 16.178	0.130
Sodium	≥ 135	157			Ref
Sodium	< 135	89	0.726	0.720	2.067	0.504, 8.478	0.313
Potassium	≤ 4.5	199			Ref
Potassium	> 4.5	47	1.213	0.801	3.365	0.700, 16.178	0.130
Serum Cr (mg/dl)	≤ 1.5	220			Ref
Serum Cr (mg/dl)	> 1.5	26	4.680	1.330	107.783	7.944, 1462.376	< 0.001
*Antitoxin	No***	47	1.246	0.810	3.475	0.711, 16.986	0.124
SEC-Socio-economic class; Diphtheria antitoxin; β- Beta coefficient; Std-Standard CI-Confidence interval, OR-Odds ratio, ref-reference value for the odds ratio; #References were “no” References were normal findings; **Reference was Yes.

Complications of Diphtheria

Of the 246 patients in this study, 83 (33.7%) developed at least one complication. Further breakdown showed that 59 patients had a single complication (59; 24.0%). The most common complications were cardiac complications (n = 42; 17.1%), followed by neuropathy (n = 31; 12.6%), and the least common was airway obstruction (n = 15; 6.1%), as shown in Table 5.

Table 5

Complications among the admitted patients
Complications	Total number of cases (246)	percent
Cardiac complications	42	17.1
Neuropathy	31	12.6
Renal impairments	15	10.2
Airway obstruction	15	6.1
Combined	83	33.7
1 complication	59	24.0
2 complications	19	7.7
3 complications	4	1.6
4 complications	1	0.4

Nigeria has experienced recurrent outbreaks of diphtheria due to low immunization coverage and healthcare challenges [8]. This study included 246 cases of diphtheria over 10 months, perhaps the largest hospital-based data from Nigeria, and highlighted the significant threat posed by the re-emerging disease. This finding translated to an average of 25 cases per month and far exceeded the total of 35 cases we reported at the same facility during the COVID-19 pandemic (July to December 2020) [3] The cases recorded at the facility also exceeded 233 diphtheria-related cases reported from acute care hospitals in Canada from 2006 to 2017 [12] Comparatively, the average monthly cases also exceeded the average of 20 cases per month reported from six hospitals in Indonesia (389 cases over 20 months) from January 2017 to August 2018 [9] In contrast, cases from this study are far less than 2,925 cases (average of 60 cases per month) reported from January 2008 to December 2012 at a referral hospital in India [13] Though less than 656 epidemiology reported cases of diphtheria by the NCDC for epidemiological week 42 (2024) and cumulative 22,293 suspected cases and 13,387 (60.1%) confirmed cases from Epi-week 19 (2022) to Epi-week 51 (2023) in the country [14], which comprise both admitted and non-admitted cases, our data supports the continuous unabating burden of diphtheria and a call to re-appraise the current strategies towards curbing the disease.

Clinical features at presentation associated with hospitalization outcomes included inability to swallow, drooling of saliva, cough, difficulty breathing, nasal discharge, nasal blockade, voice changes, nasal regurgitation, neck swelling, exudates, tonsillar enlargement, bloody nasal discharge, added heart sounds, abnormal chest findings, and hypoxemia. These features were among the variables similarly identified to be associated with outcomes among a cohort of 283 cases of diphtheria in Indonesia [9]. However, this present study's findings contrast with an earlier Nigerian study [3] where most of the clinical features were comparable between survivors and non-survivors, probably due to the sample size effect, as the present study has 246 cases compared to the earlier study, which had 35 cases. The clinical features are evidence of disease progression and disease severity, which have been identified to be related outcomes of the disease [15]. The findings of these clinical features also reinforce their continuous relevance as part of the case definition, especially in resource-constrained settings where there is limited access to diagnostic facilities.

The laboratory findings associated with hospitalization outcomes were white blood cell counts, lymphocytes, neutrophils, serum bicarbonate levels, serum sodium levels, serum potassium levels, and serum creatinine levels. Similarly, in Indonesia, white blood cells and thrombocytes were associated with hospitalization outcomes, although electrolytes were not among the variables evaluated in the study [9] In contrast, our previous study only found a relationship between outcomes and serum potassium and chloride [3] Further comparison of the current laboratory data is limited, as most studies did not report laboratory features that impact outcomes in diphtheria [2, 4]. These laboratory features are probably reflective of ongoing pathogenic responses to toxin-mediated cellular damage, with electrolyte imbalance also reflecting reduced intake due to respiratory pathologies such as pseudomembrane and an enlarged neck [7].

Immunization remains part of the key strategies to curb and prevent the spread of diphtheria, while the administration of antitoxin has also been documented to improve clinical outcomes, both of which are supported by the findings in this study [16]. Studies have documented that levels of immunization are critical in preventing outbreaks, with the higher coverage rate for diphtheria reducing the chance of an outbreak [16, 17]. The uptake of the third dose of DPT3 across Nigeria is low (about 50% of coverage for children aged 12 months to 23 months), with northwestern Nigeria having one of the lowest coverage rates (42%), which may have been part of the reasons for the continuous re-emergence of diphtheria in the region [18]. This calls for a re-appraisal of vaccination campaign strategies, ensuring rapid scale-up of routine immunization and possibly regular supplemental vaccination in the affected regions besides the outbreak immunization response. Approximately 81% of the cohort in this study received antitoxin along with other standards of care for case management, with improved outcomes, which is consistent with observations in other studies [5][19]. Antitoxin, when administered early, bind diphtheria toxins and prevent tissue damage, the main pathogenic mechanism associated with various complications.

The mortality rate in this study was 23.6%, although still high, it is less compared with studies in Nigeria [20], and India [17]. This relatively low mortality rate compared with the aforementioned studies is probably due to the impact of the administration of antitoxin (previously not available in Nigeria) and to the improved standard of care as the patients were managed in dedicated isolation wards with adequate supportive care. The number of complications in this study is also low and comparable to other countries, probably a reflection of the impact of the administration of antitoxin and improved standards of care [15, 21]

At baseline, variables that predicted hospitalization deaths were neck swelling, abnormal chest findings, hypoxemia, and elevated serum creatinine above 1.5 mg/dL. The finding of neck swelling has been well documented as a strong predictor of death in the literature and is due to enlarged cervical lymphadenitis along with soft tissue swelling [22] Neck swelling, otherwise referred to as “bull neck,” should be considered a sign of severe disease and calls for closer monitoring. We also observed abnormal chest findings [tachypnea, crackles, and reduced breath sounds], which are signs of respiratory complications at presentation and predictors of death. Respiratory complications with respiratory failure have been identified as a leading cause of death in cases of diphtheria [15] A few studies have also identified hypoxemia as a cause of death, suggesting that respiratory diphtheria, the most common form of the disease, may impair airflow, necessitating closer monitoring [23, 24]. Hypoxemia may be an indication for early airway support such as mechanical ventilation and tracheostomy as part of the standard of care, as documented in a few studies.¹⁸ This study also identified elevated creatinine at baseline as a predictor of death, which contradicts our previous publication[3]. Elevated creatinine, a sign of renal impairment, is an independent predictor of poor outcomes in many clinical conditions, including infectious diseases, and our findings suggest a significant role the renal system may play in the outcomes of diphtheria cases [25]. Diphtheria toxin has been shown to be lethal to renal tubular cells and subsequent kidney impairment.

Strengths and limitations of this study

The strength of this study included being the largest hospital-based dataset from Nigeria, and it evaluates three core areas that have been documented to impact the outcomes of diphtheria: socio-demographics, clinical features, and laboratory features. Secondly, most of the cases received antitoxin (previously unavailable in Nigeria), allowing us to see the potential impact of its administration with a significant decline in mortality compared with the previous case fatality rate in Nigeria. Third, we collected data prospectively, unlike other Nigerian studies that relied on retrospective methods. Despite these plausible reasons, this study has some limitations: it is a single-center study and may represent the tip of the iceberg on the actual burden of the diphtheria outbreak in the country. In addition, the mortality rate in this study does not reflect the actual case fatality rate in the country, as the hospital data only reflects admitted moderate-to-severe cases of the disease.

Diphtheria is a re-emerging disease that constitutes a significant burden in Nigeria, especially among children. The presence of neck swelling, hypoxemia, respiratory findings at presentation, and impaired renal function (creatinine levels above 1.5 mg/dl) are highly predictive of in-hospital death. Despite the availability of antitoxin, the hospital-based case fatality rate remains high, which calls for a re-appraisal of present strategies for mitigating the further spread of the disease in the country.

Ethics approval and consent to participate

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

This research has no grant or external funding

Authors' contributions

AA conceptualized this work, was involved in study design, data curation, literature review, data visualization, draft and approved the final version. ORI was involved in conceptualization, data curation, data visualization, data analysis, literature review, draft and critically appraised the manuscript. RMI was involved in study design, data visualization, data analysis, literature review, draft and critically appraised the manuscript. OA was involved in study design, data curation, literature review, data visualization, draft and approved the final version. ASL was involved in study design, data curation, literature review, data visualization, draft and approved the final version. YYY was involved in study design, data curation, literature review, data visualization, draft and approved the final version. AS was involved in study design, data curation, literature review, data visualization, draft and approved the final version. BMS was involved in study design, data visualization, data analysis, literature review, draft and critically appraised the manuscript

Acknowledgements

We thank the staff of Isolation ward for their care of the patients during hospitalization

Conflict of Interest

The authors have none to declared

Funding Source

This research has no grant or external funding

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No competing interests reported.

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Epidemiology of Diphtheria and Predictors of Outcome in Nigeria: A Single-Center Study from July 2023 to April 2024

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Abstract

Background:

Methods

Results

Conclusions

Introduction

Methods

Study design and setting:

Study population

Sample size

Definition of terms

Study outcomes

Data collection

Data analysis

Results

Socio-demographic characteristics of the study subjects

Clinical and Laboratory features of the study population

Factors that predicted in-hospitalization mortality

Complications of Diphtheria

Discussion

Strengths and limitations of this study

Conclusion

Declarations

References

Additional Declarations

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