Introduction

Vaccines are the most cost-effective form of medical intervention in the least developed countries, as they contributed in eliminating or significantly decreasing the occurrence of many diseases which can cause disability and death, and led to increased life expectancy [1-3]. Many childhood diseases have almost been eliminated in many developed countries primarily through the introduction of routine childhood immunization, pediatric care and improved hygiene status [3,4].

Diphtheria was a leading cause of childhood morbidity and mortality in the pre-vaccination era [5]. In the pre-vaccination era, diphtheria was a leading cause of childhood mortality. [4] Diphtheria usually affects preschool and school-age children, and is generally rare in infants and adults [6]. Globally, diphtheria has been showing a declining trend due to effective childhood vaccination programs [5]. Re-emergence of diphtheria in many countries, India [5, 7-12] Pakistan, Iran and Sudan are among the list of ten countries with the highest prevalence of diphtheria between 2010 and 2017 [13]. Recent diphtheria outbreaks in many countries, including Sudan, demonstrated a shift in the age distribution of cases to older children and adults [6,14].

A village midwife noted occurrence of a cluster of suspected cases of diphtheria in a village in Al Sunta locality in State of South Darfur, Sudan during the International Epidemiologic Week (IW) 43, she notified the State Ministry of Health (SMOH) on 4 November 2019 (IW 44). More suspected cases of diphtheria were reported from Al Sunta, Buram and Merchang localities in South Darfur. Supported by the World health Organization (WHO), the SMOH deployed a Rapid Response Team (RRT) to confirm occurrence, assess magnitude and severity of the outbreak and assist in implementation of appropriate response measures.

Methodology

The Study Area

Al-Sunta locality is located in the south-eastern part of South Darfur State, bordered to the east by East Darfur State and to the north by Geraidha locality, to the south by South Sudan and to the west by Buram locality. The locality lies at the periphery of the State with poor infrastructure. A total of 90,880 people reside in 41 scattered villages in Al Sunta locality. Children less than one year constitute 3,311 (3.64%); and under 5-year old children are about 15,441 (17%). There are sizable numbers of nomadic pastoralists, Internally Displaced Populations (IDPs) and refugees in the locality. There are neither paved roads nor electricity in the locality. There are intermittent telecommunication services. The PHC services are provided by only one health facility that belongs to the health insurance. Vaccination coverage is very low in Al Sunta locality. The Penta 3 coverage was 37%, 75%, and 91% for the years 2016, 2017 and 2018 respectively [15]. Currently, Penta 3 coverage stands at 33% in 2019 [10]. A laboratory confirmed outbreak of diphtheria was reported from Al Salam locality in South Darfur in 2018 (Figure 1).

Figure 1: Map of Al-Sunta locality.

Data collection

A suspected case of diphtheria was defined as any child or young adult who complained of moderate fever, sore throat, unilateral or bilateral swelling of the neck, enlarged tonsils, and or epistaxis and mild exudative pharyngitis during the month prior to the visit of the investigation team. The investigation team ascertained the vaccination history and examined suspected cases and contacts for presence of pseudo-membranes form in the throat. Presence of grey membrane was considered as a clinically confirmed case. Verbal autopsy was taken from parents of the deceased children using case definitions and extra probing questions to confirm or rule out the diagnosis of diphtheria. Parents were asked about questions related to cardiac (chest pain) and neurological manifestations. The investigation team asked about occurrence of similar cases among neighbors or acquaintances. Local names of the disease were used to identify active cases in the community (Dignn daier, Al-Khannag, Abu Hilaig). The active case finding was based on a line listing of the reported suspected cases.

A total of 111 laboratory specimens (52 oropharyngeal and/or nasopharyngeal swabs and 59 5-ml blood samples) were collected from suspected cases, close contacts and recovered cases by trained physicians or a laboratory technician. Ames transport media was used for swabs while clotted blood samples were separated and serum collected. All specimens were kept in ice packs in sample carrier during the field visit. Samples were transported by road to Nyala, Capital City of the State, and were shipped to the National Public Health Laboratory (NPHL) in Khartoum for confirmation of diagnosis. Polymerase Chain Reaction (PCR) was used to differentiate toxigenic and non-toxigenic diphtheria.

The investigation team used structured and open ended questionnaires to guide interviews and Focus Group Discussions (FGDs) to stimulate discussion and allow for probing questions. The key informants included Director General, State Ministry of Health (SMOH), Expanded Program on Immunization (EPI) Director, SMOH, EPI Officer in Buram locality, and Medical Assistants in Buram and Al Sunta localities. The investigators also held series of Focus Discussion Groups (FGDs) with community leaders in fifteen villages that reported suspected cases of diphtheria and associated deaths. The team conducted an expanded FGD with nomadic pastoralists who attended the weekly market in Tajreeba Town. The team asked for regular pathways and season of nomadic pastoralists’ movement. Two major schools in the area (boys and girls) were visited to identify additional unreported cases of diphtheria, vaccination history and absenteeism from school. The ad hoc surveys included 111 male schooled children in Tajreeba School in Al Sunta locality.

Interviews and FGDs were videotaped and transcribed.

Parents and healthcare workers were asked to describe in detail the sequence of symptoms and progression of the disease, the medical care and related events. Parents were also asked about the history of vaccination of their children using quick ad hoc survey in Tajreeba market. Community members were asked if vaccinators were visiting their areas. Probing questions were asked regarding the circulating rumors on animal deaths and pesticides sprayed to kill migratory birds in the area.

While visiting the health facilities, the investigators observed and reviewed logbooks at Family Health Units (FHUs) to look into the reports, feedback, and defaulters tracing mechanisms. The team observed functionality of the cold chain systems and potency of the vaccines. Treatment regimens used to manage suspected diphtheria cases were also reviewed. The team visited Nyala Teaching Hospital to assess the capacity and preparedness for case management including presence of an isolation ward. The team assessed the capacity, availability and functionality of State Public Health Laboratory (SPHL) in terms of staff, equipment, reagents, and consumables. The investigators reviewed the recent Simple Spatial Survey Method (S3M) and the EPI data for South Darfur State to assess the immunization coverage.

Results

Confirmation of the outbreak

The index case was a 7-year old girl from Um Baighla village in Al Sunta locality on International epidemiologic Week (IW) 42. She demonstrated symptoms and signs consistent with case definition of a probable case of diphtheria. She had been playing with the son and daughter of a farmer from Um Kitaika; the boy developed similar symptoms on IW 43 and spread the disease in Um Kitaika. All of the three primary cases died.

As of 04 March 2020, a total of 97 probable cases of diphtheria were reported by the disease surveillance system: 36 males (43.6%) and 31 girls (56.4%); the female: male sex ratio was 1.3. The diagnosis of diphtheria was clinically and laboratory confirmed. Toxigenic Corynebacterium diphtheria was identified by culture and Polymerase Chain Reaction (PCR) from one out of six pharyngeal swabs collected by the RRT. Most of the cases occurred among fifteen neighboring villages around Al Sunta locality, mainly Um Kitaika village and Tajreeba town.

In two of the households visited, they reported three cases and two deaths from same house. There were no cases reported among nomadic pastoralists in the locality. Of all cases, 90 (92.8%) were not vaccinated. The mean age (N. SD, IQR, was 12.5 (61, 8.6., 7.0-16.0) and 11.0 (36, 6.0-13.5) for females and males respectively; the difference was not statistically significant two-tailed p value=0.3608. Twelve cases died (Case Fatality Ratio (CFR) = 12.4%).

Most of the cases occurred among neighboring villages around Al Sunta locality. there were three cases and two deaths from same house. There were no cases reported among nomadic pastoralists. Most of the suspected cases were not vaccinated (No data were available).

Figure 2 shows the epidemic curves of the diphtheria outbreak in South Darfur, 2019. The outbreak spread serially from one village to another. More cases occurred in a large village, Um Kitaika and a small town I the locality, Tajreeba.

Figure 2: The epidemic curves of the diphtheria outbreak in South Darfur, 2019-2020.

Parents of suspected diphtheria cases and deceased children stated that their children had high grade fever, sore throat, dysphagia (difficulty in swallowing), neck swelling, protrusion of the tongue and some children suffered from difficulty in breathing. The symptoms got worse on the third day following onset of the disease. Later, some patients complained of discharge from the mouth and epistaxis. Verbal autopsy from parents of the deceased children reported that children were suffering from severe chest pain just before death. There were no neurological symptoms observed or reported. The health care workers mentioned that the tonsils were excessively enlarged among few of the cases, almost touching each other. They reported observation of grey membrane behind the tonsils in some of the cases.

Low immunization coverage

The cold chain system in Al Sunta was not functioning for more than three years. Vaccines were kept in refrigerators in nearby shops along with soft drinks. The vaccinator stated that he reported the case to EPI department repeatedly with no response. The investigators found out the Vaccine Vial Monitor (VVM) reading of the vaccines stored in the private refrigerator was almost stage 3. In Rammis village, Al-Sunta locality, a cold chain system was installed in the Family Health Unit (FHU) in May 2019. There were no means of transportation to conduct outreach vaccination services. More defaulters were registered in Al Sunta and Buram localities (Figure 3).