Cholera

Cholera is unique among waterborne bacterial infectious diseases in its potential to cause pandemics. Over the last 200 years, the world has witnessed 7 pandemics of cholera. We are currently in the second and the third waves of the seventh cholera pandemic attributed to a Vibrio cholerae O1 el Tor strain.Reference Harris, LaRocque, Qadri, Ryan and Calderwood ⁷ Notably, the second wave of the seventh pandemic was associated with the acquisition of additional antibiotic resistance, and the third (ie, current) wave has been associated with the acquisition of a cholera toxin variant; both of these are major concerns and could lead to a global public health disaster.Reference Mutreja, Kim and Thomson ⁸

Cholera outbreaks occur in the background of poor sanitation and inadequate access to clean drinking water.Reference O’Connor, Cartwright and Loharikar ⁹ This setting has been the hallmark of the perpetuating civil wars in Iraq, Syria, and Yemen, whereby water and sanitation management as well as infrastructure have been damaged either intentionally or accidently. For example, the 2015 cholera outbreak in Iraq is thought to be related to the low water levels in the EuphratesReference Hameed and Kalin ¹⁰ as well as the winter flooding, which likely contaminated the Euphrates River and shallow wells with sewage water (Table 1). Two previous outbreaks in Iraq, noted to be of a lesser severity, were reported during 2007 and 2012 and had similar environmental commencements. They affected the northern governorates including Babel, Baghdad, and Kerbala. ¹¹

Table 1 Cholera Outbreaks Associated with Conflict in the Middle East

Between September and November 2015, the WHO reported a severe cholera outbreak in Iraq, with >5,000 confirmed cases and several deaths. ^{12 ,} Reference Lam, Al-Tamimi and Russell ¹³ However, the WHO representatives in these areas admit to underreporting because of logistic surveillance difficulties, particularly in the active war zones.

Some reports indicate that this cholera outbreak has spread to neighboring Syria, Kuwait, and Bahrain, with a risk of turning this localized outbreak into a region-wide epidemic. ¹⁴ The areas where the largest numbers of cholera cases have been detected include the Shiite cities of Najaf and Karbala, where millions of Shiite Muslims travel annually on religious pilgrimages to their holy shrines.

In response to the 2015 outbreak, the Iraqi Ministry of Help with the assistance of international governmental agencies (IGOs), initiated a vaccination campaign targeting at least 255,000 people, mobilizing the largest oral cholera vaccine (OCV) stockpile and providing supportive care and educational benefits to raise awareness.Reference Lam, Al-Tamimi and Russell ¹³ The outbreak seemed to have subsided by December 2015.Reference Lam, Al-Tamimi and Russell ¹³ However, among the people who received immunization, the proportion that received the 2 full vaccinations was estimated to range from 21% to 90%. This lack of vaccination coverage is thought to have been influenced by several critical factors including lack of compliance, the continuing displacement of individuals, and the shortage of the vaccination supplies.Reference Lam, Al-Tamimi and Russell ¹³

For the past 3 years, the ongoing civil war in Yemen has highly impacted the basic public health sanitation infrastructure of this country, manifesting a cholera outbreak. This outbreak was first reported in October 2016, and the number of suspected cases exceeded 1,051,789 individuals by January 2018. This phenomenal increase reported by the WHO and the Yemen Ministry of Public Health makes this cholera outbreak the largest epidemic in the world. ¹⁵ Vital public health infrastructures in civilian areas have been totally destroyed or made inoperable, resulting in massive displacement of the affected population into crowded and unsanitary conditions.Reference Kennedy, Harmer and McCoy ¹⁶ Currently, ~2,000 attributable deaths have been reported, and the outbreak has extended geographically, affecting nearly all the governorates in the country. ^{15 , 17}

The WHO and Yemen partners in the Global Health and Global Water Sanitation and Hygiene Cluster (WASH) or Global WASH cluster (GWC) have responded by providing medical supplies such as diagnostic kits, rehydration solutions, and chlorination tablets, to hospitals handling cholera cases. Small interventions like these are not costly and are capable of decreasing fatality rates among infected patients by 50-fold.Reference Zaidi ¹⁸ These organizations have also supported the opening, rehabilitation, and maintenance of more than 39 diarrheal treatment centers. ¹⁹ As a result of these interventions, the incidence of cholera began declining and continued to decline until May 2017, when an upsurge in cases was noted. This reversal is believed to have occurred after a catastrophic failure of the sewer system in Sanaa was caused by continuous airstrikes on the city coincident with the beginning of the rainy season. These factors, in addition to severe malnutrition, contributed to the increased morbidity of the disease.Reference Kennedy, Harmer and McCoy ^{16 , 20} The weekly surveillance cases had been decreasing for the preceding 20 weeks, as reported in late January 2018. ¹⁵ This decreasing trend occurred despite the fact that the 1 million doses of the oral cholera vaccine that had been allocated from the global stockpile were cancelled in July 2017 due to fear of the vaccine’s ineffectiveness and the realization that the large volume of people at risk dramatically exceeded the supply.Reference Wadman ²¹ This move could have been of benefit had it been done earlier in the course of the crisis. Apparently, vaccination plans with a more adequate amount of vaccine to be allocated are still being researched.Reference Qadri, Islam and Clemens ²²

One potential solution to the previous vaccination issues is the newly approved single-dose oral cholera vaccine (Vaxchora), which could provide the needed efficacyReference Herzog ²³ and improve compliance by providing a single dose of the vaccine rather than the conventional 2 separate dose vaccinations required. This solution has been hindered, however, because the effectiveness of Vaxchora has not been established in persons living in cholera-affected areas, and the vaccine’s effectiveness has not been established in persons who have pre-existing immunity due to previous exposure to V. cholerae or who previously received a cholera vaccine.

The WHO, in collaboration with United Nations Office for the Coordination of Humanitarian Affairs (UNOCHA), the European Commission’s Humanitarian Aid Office (ECHO), and the Office of Foreign Disaster Assistance (OFDA), are working on optimizing their surveillance systems to be able to detect, investigate, and intervene adequately when an outbreak is suspected. ²⁴ The WHO and partners recently directed a cholera risk assessment program to classify cholera into 4 risk categories based on (1) population density, (2) access to clean water and sanitation, (3) level of service in camps, and (4) direct exposure to conflicts. This effort aimed at predicting future outbreaks during these presumably high-risk periods. ²⁵

Poliomyelitis

In 2014, the WHO estimated that more than 7,600 Syrians were infected with poliomyelitis, with subsequent spread of the infection to Iraq (Table 2).Reference Arie ²⁶ This outbreak occurred after 15 years of eradication of poliomyelitis in Syria during the preconflict era.Reference Abroug, Slim and Ouanes-Besbes ²⁷ Most of the polio reported in Syria occurred in the northeastern province of Deir El Zur, which was the epicenter of the outbreak.Reference Arie ²⁶ However, several other cases were reported in the rural areas of Damascus, Aleppo, and other rural regions.

Table 2 Viral Outbreaks (Polio/Measles) Associated with Conflict in the Middle East

Poliomyelitis is a virus that lives in sewage-contaminated water and food. Hence, several war-related factors contributed to this poliomyelitis outbreak. First, particularly during the war, raw sewage was pumped directly into the Euphrates River, which provides drinking and wash water to many villages. This occurred simultaneously with the discontinuation of chlorination of previously potable water.Reference Sparrow ²⁸ Second, poliomyelitis is a vaccine-preventable disease, and the vaccination coverage in Syria dropped from ~91% in 2010 before the conflict to as low as 45% by 2013.Reference Mahjour ³ An estimated 58% of the polio cases reported in children during the outbreak in Syria and Iraq had never received the polio vaccine.Reference Mbaeyi, Ryan and Smith ²⁹ Third, several boosters of polio vaccines are required to confer protective immunity, which impedes the success of polio vaccination programs. Incomplete vaccination was reported in 37% of the children with polio in Syria and Iraq in October 2013.Reference Mbaeyi, Ryan and Smith ²⁹ In addition to the war-related factors described above, overcrowding of tens of thousands of displaced and refugee populations inside and outside Syria has occurred. This population has limited healthcare access, unsanitary living conditions, and limited (or no) access to communicable disease vaccinations.Reference Sharara and Kanj ¹

In addition, the strain of poliomyelitis in Syria has been linked to a wild-type strain found in Pakistan, which is suspected to have been introduced into Syria by a jihadist fighter from Pakistan.Reference Eichner and Brockmann ^{30 ,} Reference Foot ³¹ The dissemination of this virus within the region has also been reported; cases of polio have been described in Lebanon, Jordan, as well as Iraq. ³² Polio in Syria has been declared a public health emergency that requires international efforts and solidarity to prevent a global epidemic. Fortunately, this outbreak was successfully contained and interrupted within 6 months through the implementation of proper surveillance measures. After multiple vaccination campaigns in Syria, monitoring coverage improved from 79% in December 2013 to 93% in March 2014.Reference Mbaeyi, Ryan and Smith ²⁹ The last case of polio in Syria was reported in January 2014. A similar positive response was also seen in Iraq. In addition to providing humanitarian aid, health hygiene, clean water and sanitation, as well as facilitating healthcare delivery and vaccination, a high level of systematic surveillance should be maintained to prevent further outbreaks.Reference Mbaeyi, Ryan and Smith ^{29 ,} Reference Al-Moujahed, Alahdab, Abolaban and Beletsky ³³

No polio cases have been documented in Yemen since the beginning of the conflict. To maintain the polio-free status achieved in Yemen in 2006, and after the last immunization campaign in April 2016, a nationwide polio immunization campaign was launched in February 2017, targeting the general population and particularly children in high-risk groups. ³⁴

Measles

Measles is a highly contagious viral illness that has a high efficiency of airborne transmission, but the disease is vaccine preventable. A measles epidemic has been reported in Syria during the current period of unrest, particularly in the northern regions of the country such as Aleppo. An estimated 7,000 cases have been reported by the WHO and Médecins Sans Frontières (MSF) organizations: ~200 cases in 2013; 4,309 in 2014; 1,617 in 2015; only 85 cases in 2016; and an upsurge in 2017 with 733 laboratory-confirmed cases (Table 2). ^{35 , 36} The measles epidemic disseminated to neighboring countries such as Jordan, where 24 cases were reported in 2012 and >4-fold more (>200 cases) were reported in 2013.Reference Nimer ³⁷ These estimates declined to 38 by 2015. In addition, only 9 cases were reported among the Lebanese population in 2012, but this number increased to 1,760 by 2013. Then, the reported numbers of measles cases went down to 205 in 2014, to 39 in 2015, and to 44 in 2016. Such trends have been similar among the Syrian refugees in Lebanon: 232 measles cases were reported in 2013, 107 in 2014, 12 in 2015, and 18 in 2016. ³⁸

Moreover, a decline has been documented in the rates of measles vaccinations in Yemen, which has reached as low as 41%.Reference Qirbi and Ismail ³⁹ This vaccination decline resulted in increased numbers of cases, with >847 measles cases by December 2011; 2,143 cases in 2012; and 1,634 cases in 2017. ^{40 , 41}

Measles vaccination rates dropped nationwide in Syria from a stable rate of 82% in 2010 to as low as 53% in 2015, dipping to 17% in some northern cities like Kobanî. ^{42 , 43} Through December 2016, an estimated 4.56 million children had been immunized against measles in the accessible areas of the Syria, but despite all efforts, the national vaccination rates have remained low, reaching only 65% for 2016. ³⁵ To address this void, the WHO held health education conferences in areas considered to be at high risk because the resistance of parents hindered the immunization campaigns. ^{35 , 36} Unfortunately, a muscle relaxant (atracurium) was accidently mixed up with a diluent used with the measles vaccine and caused the deaths of 17 children, thus causing further anxiety for parents needing to vaccinate their children.Reference Pakenham-Walsh and Ana ⁴⁴

Vaccination campaigns are critically important to vulnerable populations in these areas of the world. However, the escalating conflicts in the northern areas of Iraq and Syria, as well as Yemen, are hampering these immunization campaigns significantly.

Leishmaniasis

Leishmaniasis is transmitted to humans by the bites of infected female phlebotomine sand flies, and it constitutes a major public health problem in the eastern Mediterranean region (EMR). ⁴⁵ Four types of Leishmania spp cause most of these infections in humans; cutaneous leishmaniasis accounts for the largest number of cases. Globally, the estimated numbers of cases of leishmaniasis annually are 12 million for cutaneous leishmaniasis and 2.5 million for visceral leishmaniasis. Also, an estimated 1.5 million cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis are reported annually among 88 countries. ^{45 ,} Reference Al-Kamel ⁴⁶ The EMR is an ill-defined geographical region in which most countries have experienced some form of hostilities or civil war over the past 20 years, whether major invasions, internal strife, or cross-border clashes. This unrest has led to massive movements of populations, including refugees and military personnel, which have contributed to several outbreaks of cutaneous leishmaniasis.

For decades, cutaneous leishmaniasis has been recognized as a skin-deforming infection transmitted by a sand fly. It is endemic in northern Syria, particularly Aleppo and Damascus.Reference Sharara and Kanj ¹ However, with the recent conflict in Syria, increasing violence from civil war, and terrorist activity leading to vast population displacement, an epidemic in 2012 involved >52,000 confirmed cases (Table 3).Reference Burki ^{47 ,} Reference Hayani, Dandashli and Weisshaar ⁴⁸

Table 3 Leishmaniasis Outbreaks Associated with Conflict in the Middle East

Despite leishmaniasis being endemic in Lebanon, a cutaneous leishmaniasis outbreak began among Syrian refugees in Lebanon in September 2012, and by 2013, 1,033 cases had been confirmed; 97% of them were among Syrian refugees. The average age of these patients was 17 years, with 80% being <18 years old.Reference Pakenham-Walsh and Ana ^{44 ,} Reference Saroufim, Charafeddine and Issa ^{49 ,} Reference Alawieh, Musharrafieh, Jaber, Berry, Ghosn and Bizri ⁵⁰ In this particular outbreak, 85% of the cases were caused by L. tropica, a species epidemic to Aleppo that causes aggressive large, disfiguring lesions and a prolonged disease course that necessitates intramuscular treatment.Reference Saroufim, Charafeddine and Issa ⁴⁹ The Lebanese Ministry of Public Health, in collaboration with the WHO, launched a coordinated campaign to contain the spread of this infection, which included spraying pesticides to kill the vector, providing free treatment and diagnosis for new cases, establishing a referral system with 12 treatment clinics across Lebanon, and producing public awareness and health education materials.Reference Sharara and Kanj ¹ However, controlling the source of this infection in northern Syria, particularly in and around Aleppo, has not been possible because of the conflict in that area. Recently, due to different war-related factors, new outbreaks have been reported from different areas bordering Syria, including Turkey and Iraq. ⁵¹

Cutaneous leishmaniasis is a neglected disease in Yemen due to the lack of awareness of the natural course of the disease and the possibility of medical treatment. Despite poor documentation and underestimation of its burden, this disease seems to be endemic in this country—it occurs nationwide.Reference Al-Kamel ⁴⁶ The interruption of healthcare services, the poor housing conditions, the current armed conflict in Yemen, the human migration from cities to villages, the arrival of refugees from other endemic countries such as Iraq and Syria, the absence of active detection and national reporting systems, and the lack of systematic national efforts to control the disease are all risk factors for enhanced transmission of cutaneous leishmaniasis in Yemen.Reference Al-Kamel ⁴⁶ Effective treatment accompanied by measures for prevention of reinfection should reduce the incidence of anthroponotic cutaneous leishmaniasis. Control of cutaneous leishmaniasis in Yemen should be based on the best knowledge of the Leishmania parasite species and of different reservoir hosts and vector behaviors so that effective control measures can be undertaken. To address the problem of leishmaniasis in the EMR in the future, collaborative efforts with the WHO and supporting ministries of health of the regions should be undertaken through a strategic plan that includes the following measures: establishing a regional surveillance system, implementing training strategy, allocating appropriate resources for early detection, providing free medication, and facilitating subregional collaboration.Reference Postigo ⁵²

Diphtheria

Diphtheria is a bacterial infection caused by Corynebacterium diphtheria that can result in respiratory and cutaneous diseases. It can be transmitted through respiratory secretions or skin lesions of affected patients or asymptomatic carriers. Since the introduction of the diphtheria vaccine, the disease has become rare in developed countries. However, diphtheria is resurging in developing countries as a result of poor socioeconomic status; compromised healthcare infrastructure; poor access to care; and shortages of vaccines, antitoxins, and antibiotics. In addition to the other disease outbreaks reported in Yemen, the WHO and Reuters have reported a large outbreak of diphtheria affecting close to 500 people since August 2017, with rapid spread in multiple governorates and a high fatality rate of 10%, particularly in children. ^{53 –} Reference Nebehay ⁵⁵ The armed conflict and imposed blockade of Yemen’s ports has resulted in shortages of food and medical supplies, poor access to care, the inability to perform the required diagnostic laboratory testing, and a decline in the rate of vaccination (>60% of the suspected cases had not received any vaccination). The MSF are working with the WHO to allow diagnostic laboratory testing on suspected cases to identify cases that require isolation, to provide treatment and antitoxins, and to provide prophylaxes to the patients’ close contacts.

Other infectious diseases

Clusters of hepatitis A outbreaks have been reported during the Syrian conflict over the last 2 years, particularly among displaced Syrian populations. An outbreak of hepatitis A among Syrian refugees in northern Iraq in 2013 was halted by the efforts of the WHO, other international organizations, and local health authorities to improve conditions in the camps. ⁵⁶ Across Syria, 49,300 cumulative cases of hepatitis A were reported in 2015. ³⁵

In addition, other infectious diseases, such as multidrug-resistant tuberculosis, have been reported, particularly in association with the Syrian crisis. Lebanon has reported a 27% increase in the incidence of TB attributable to the Syrian refugees.Reference Ismail, Abbara and Collin ⁵⁷ The Al Noor Chest Disease Sanatorium in northern Jordan has reported high rates of tuberculosis, including multidrug-resistant tuberculosis, among Syrian refugees who are seen in its outpatient clinics.Reference Ismail, Abbara and Collin ⁵⁷ In Jordan and Turkey, this population does not have access to public health care at Ministry of Health facilities, ⁴⁵ which puts refugees at higher risk of contracting and transmitting the disease.

In conclusion, given the catastrophic implications of these infectious disease epidemics in the Middle East, both at the regional and the global levels, a concerted collaborative effort needs to be initiated that joins the WHO and relief governmental agencies on one side with IGOs and NGOs on the other.

Numerous unanswered questions could be raised regarding Middle East countries amid civil conflicts, and several limitations to our data should be considered. Unfortunately, countries under the siege of conflicts face difficulty collecting data, particularly from combat zones, destroyed areas, and displaced people. Therefore, the proper analysis of the actual impact of the conflicts in the re-emergence and spread of the infectious diseases, the assessment of the postconflict needs, as well as the results of the targeted interventions, should be undertaken by IGOs in collaboration with NGOs to evaluate the capacity of the health system and its functionality in the postconflict era. Without a structured surveillance system and/or mandatory reporting mechanism, most, if not all, of the highly communicable diseases will continue to disseminate and be underreported, especially in the background of regional conflicts and displaced refugees. Although there could be a correlation between emerging infectious diseases and failing healthcare systems, identifying a direct association without good surveillance systems or hard measurable data is challenging.

Governments should take responsibility by acknowledging the early appearance of these emerging diseases, which plays a tremendous role in prevention and management. Denying and hiding the initial signs of disease dissemination have been reported throughout history in different settings all over the world.Reference Zaidi ¹⁸ Regional cooperation should be enhanced, and communication among various agencies providing healthcare and relief through the establishment of large network should be facilitated to disseminate information and share expenses.

The opportunity certainly exists to provide public health resources and structured support for the civilian populations in these war-torn areas to address their needs. The international community, including medical professionals and infectious disease specialists, can have a positive impact by alleviating the suffering of millions in this region. Providing access to clean water, improving sanitation and hygiene, supplying medications, establishing mass vaccination campaigns, supporting medical staff, offering access to health care, and instituting surveillance programs are of paramount importance to the prevention, diagnosis, treatment, reporting, and control of infectious disease outbreaks.