Massive diphtheria outbreak among Rohingya refugees: lessons learnt

Since August 2017, extreme violence in Rakhine State, Myanmar, has driven about 706 000 Rohingya refugees including 381 240 children, across the border to Bangladesh. The cumulative total (including a previous 213 000) of the 919 000 Rohingya population now living in Cox’s Bazar, Bangladesh, is congregated over a mere 6000-acres of already deforested vulnerable land.1 The speed and magnitude of influx made it the world’s fastest growing refugee crisis and a major humanitarian emergency. The Rohingyas are a persecuted ethnic group, denied citizenship in their country of birth, including access to healthcare and mainstream education since 1982, and have periodically faced violence by forces over generations, which has rendered them seriously vulnerable, even before the most recent crisis. Although the Government of Bangladesh (GoB), with support from UN Organizations, Development Partners, International Non-Government Organizations (INGO), local charities and volunteers, is working rigorously to ensure basic needs such as shelter, food, water, sanitation and healthcare, health needs are not fulfilled, creating widespread vulnerability to infection and epidemics. Inadequate water and insufficient sewage infrastructure are spreading food- and waterborne diseases, and a booming mosquito populationis leading to the spread of malaria, dengue and chikungunya infections. The Rohingya refugees are already vulnerable to infections, including vaccine-preventable diseases, due to malnutrition and low immunization coverage (only 23.2% of children under 5 years received measles vaccine2). To support the Ministry of Health and Family Welfare (MoH&FW), Bangladesh, health humanitarian actors are working through a ‘Health Cluster’ led by the WHO.3 A series of outbreaks of acute watery diarrhoea, measles and diphtheria raged through the camps, challenging the capacity of healthcare-providing organizations. Here we report on a large-scale diphtheria outbreak that started in early November 2017, which peaked around New Year’s Eve, and continues to spread till now, including among host communities. Diphtheria is a highly contagious disease that spreads from person to person generally through respiratory droplets and by direct exposure to lesion exudates. Following its entry through the respiratory system, the bacterium releases a toxin that causes weakness, sore throat, fever and swollen lymph nodes. Respiratory disease may be nasal, pharyngeal or laryngeal or any combination thereof, with pharyngeal diphtheria being the most common form. If the toxin enters the bloodstream, it may also cause damage to the kidneys, heart or nerves. According to the revised case definition, a suspected case of diphtheria is defined as ‘an illness characterized by laryngitis or pharyngitis or tonsillitis and adherent membrane of the tonsils, pharynx or nose or if the clinician has high index of suspicion’.4 The disease can also present as an indolent, non-healing skin ulcer (cutaneous diphtheria). Diphtheria transmission can be prevented through vaccination, and infection can be treated using diphtheria antitoxin (DAT) and/or antibiotics.4 Vaccination includes a primary series of three doses of diphtheria toxoid-containing vaccines, with the first dose administered as early as 6 weeks of age. Subsequent doses should be given with an interval of at least 4 weeks between doses. Diphtheria booster doses should be given in combination with tetanus toxoid at 12–23 months, 4–7 years and 9–15 years of age, using age-appropriate vaccine formulations. Given the increasing life expectancy worldwide, it remains to be determined whether a booster dose is necessary later in life. One study showed that a single booster is sufficient.5 Administration of the first three doses of diphtheria toxoid-containing vaccine together with other childhood vaccines does not interfere with the response to any of these antigens. CRM-conjugate vaccines (such as Hib, pneumococcal and meningococcal vaccines) can be administered with or before, but not after, diphtheria toxoid-containing vaccine.4,6 Intramuscular administration of equine-derived DAT (polyclonal IgG antibody) is highly effective and is the gold standard for diphtheria treatment. To reduce complications and mortality, DAT should be administered as soon as possible after disease onset, preferably intravenously in serious cases. Antibiotics (penicillin or erythromycin) eliminate the bacteria and toxin production, prevent further transmission to uninfected individuals and limit carriage that can persist even after clinical recovery.4 Airway management is crucial, including tracheotomy or mechanical removal of trachea–bronchial pseudo-membranes and/ or intubation. Extracorporeal membrane oxygenation may be required. Post-exposure prophylaxis of susceptible contacts includes active immunization with diphtheria toxoid-containing vaccine. Unvaccinated contacts should receive a full course of diphtheria toxoid-containing vaccine, and under-vaccinated contacts should receive the doses needed to complete their vaccination series. Ideally, swabs should be taken from contacts to check for Corynebacterium diphtheriae, and a course of penicillin or erythromycin should be administered for 7 days. DAT is not recommended for post-exposure prophylaxis.4 Due to the widespread use of vaccine globally, the incidence of diphtheria has steadily declined over time. Hence, diphtheria is perceived as a ‘disease of the pre-vaccination era’. Consequently, many physicians in most countries, including Bangladesh, have never seen a case of diphtheria and may fail to consider it in the differential diagnosis. Nevertheless, sporadic cases and even epidemic outbursts are often reported, especially in politically unstable areas where there are pockets of unvaccinated populations, and each year ~ 5000 cases of diphtheria are still reported worldwide.4 In recent years, India has accounted for a substantial proportion of global burden of diphtheria,7 while the largest outbreak in the past decades was reported from the Russian Federation and former Soviet Republics in the 1990s, with more than 1 570 000 cases and 5000 deaths.4 Since late 2017, there have been multiple diphtheria outbreaks in Rohingya refugee camps, making it one of the largest sustained epidemics in recent times. By the end of August 2018, 8179 diphtheria cases were reported through the Early Warning And Response System, including 271 confirmed infections, 2700 probable and 5208 suspected cases. A total of 44 diphtheria patients (confirmed and suspected) have died from the beginning of the epidemic till end September 2018 (case fatality rate <1%). A total of 183 cases with no deaths have been reported among the host community (of whom 24 were PCR positive). Since January 2018, diphtheria cases among the refugee population have declined. However, there appears to be a plateauing in the weekly case count. Cases among the host communities are being continued to be reported.8 The Rohingya outbreak showed a steep rise in the number of cases, indicating extreme vulnerability of children in the Rohingya camps and settlements (Fig. 1). Approximately 67% of the cases were <15 years, about 13% <5 years, 56% were females, 35% had pseudo-membranes, 32% had lymphadenopathy and 1% had systemic complications. The majority of them were not vaccinated against any diseases, as they had very limited access to routine healthcare back in Myanmar. This outbreak demonstrates the potential for more severe outbreaks since the population has both a large number of non-immune adults and unvaccinated children. Antibiotics were used in >65% of suspected cases and DAT in 18%.8 Epidemic cases of diphtheria in Cox’s Bazar by date of admission (Week 44, 2017–Week 22, 2018) Three rounds of vaccination campaigns were carried out in Rohingya refugee camps (December 2017, January–February 2018 and March 2018), targeting children <15 years of age. A diphtheria vaccination campaign for the host community was also carried out in January and February 2018. An immunization campaign with a booster dose of Penta/Td was conducted for the host community, targeting children 1 to <15 years of age. Case management is ongoing for every diphtheria patient, including contact tracing and chemoprophylaxis. Issues with vaccination refusal exist for various reasons, including fear of adverse effects following immunization. Following the vaccination, there was a significant drop in new cases. However, in Cox’s Bazar, diphtheria cases continue to be reported amongst both refugee and host populations at a level of 30-50 suspected cases per week. PCR-positive cases are currently being detected at a rate of 2-4 cases per week.8 Contact tracing and early identification of people suspected of having diphtheria symptoms has been the key in helping to curb transmission. Contact tracing efforts and chemoprophylaxis for contacts of all cases that fit the standard WHO case definition have been strengthened in all areas of the camp. This was a critical intervention that helped curtail diphtheria transmission. At present, all household contacts are provided with prophylactic antibiotics. Community volunteers visit the patients’households to provide antibiotic treatment to everyone and recommend that all household contacts are vaccinated. Households are re-visited on day 4 to check completion of antibiotic prophylaxis with follow-up of the vaccination status of patients after 30 and 60 days. In addition, a dose of Td vaccine is given to all contacts accompanying diphtheria patients to the health facility. Large households, contacts with a known case and child-caring adult women are at a greater risk of diphtheria. Surveillance recommendations include ensuring field surveillance covers the entire camp, strengthening laboratory surveillance and continued chemoprophylaxis of adults in the households of patients. The crisis is not over. Almost 1 million refugees and host populations need to ensure their health and well-being, and the comprehensive effort needs a long-term planning. A long-term plan would be important to prevent complex emergencies among the Rohingya refugees. Diphtheria outbreaks have recently also been reported in other conflict settings such as Yemen, and in Venezuela.9,10 Several lessons can be learnt from this massive outbreak. With a limited number of suppliers, production lead time, variable product quality and unpredictable demand as a result of outbreaks, there is a need to ensure rapid access to DAT for the treatment of diphtheria cases. An additional consideration is the absence of quality-assured products compliant with the required quality standards. WHO specifications recommend 10 000 IU/vial, but product testing indicates that some products show lower potency levels, sometimes reaching only 50% of the required levels (SAGE meeting October 2018).11 The unpredictable nature of diphtheria calls for stockpiling of quality-assured DAT. Clearly, the most efficient strategy will be to ensure universal coverage with diphtheria vaccination through expanded immunization programmes. Conflict of interest: None declared.