policy ct 14

VIEWPOINTS

Hajj, Umrah, and the neglected tropical

diseases

Mashal M. Almutairi 1,2,3,4*, Waleed Saleh Alsalem5, Mazen Hassanain4,6, Peter

J. Hotez 4,7,8,9*

1 Prince Naif Health Research Center, King Saud University, Riyadh, Saudi Arabia, 2 Department of

Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia,

3 Vaccines and Biologics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia,

4 Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine,

Baylor College of Medicine, Houston, Texas, United States of America, 5 Center for Neglected Tropical

Diseases, National Health Laboratory, Saudi Ministry of Health, Riyadh, Saudi Arabia, 6 Department of

Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia, 7 James A. Baker III Institute of

Public Policy, Rice University, Houston, Texas, United States of America, 8 Scowcroft Institute of

International Affairs, Bush School of Government and Public Policy, Texas A&M University, College Station,

Texas, United States of America, 9 Department of Biology, Baylor University, Waco, Texas, United States of

America

* [email protected] (PJH); [email protected] (MMA)

Introduction

Together, the Hajj and Umrah rank among the leading global venues that host annual mass

human migrations. The Hajj is an annual pilgrimage to the Islamic holy city of Makkah in

Saudi Arabia (Fig 1). It is considered a religious obligation for all adult Muslims worldwide

who have the physical and financial ability and draws an estimated 2–3 million people annually

[1]. Umrah is an Islamic pilgrimage to Makkah, which occurs at times other than the period of

the Hajj—the period of Ramadan (fasting month) is considered the peak period [2]. In 2018,

the Hajj is scheduled to take place in August, while Ramadan will occur between May and

June [2].

Through the Hajj and Umrah, it is estimated that visitors to Saudi Arabia arrive from almost

every country, based on a ratio of “one pilgrim per 1,000 Muslims from that country” [2]. Cur-

rently, the largest countries in terms of Muslim populations are Asian nations located in tropical

disease–endemic areas, led by Indonesia, Pakistan, India, and Bangladesh, followed by Nigeria

and Egypt in Africa, where neglected tropical diseases (NTDs) are also widespread (Table 1) [3].

Together, these nations account for almost 700,000 Hajj pilgrims, and according to the Global

Burden of Disease Study, they account for some of the largest numbers of people living with

NTDs [4].

The largest numbers of Hajj immigrants are from South and Southeast Asian tropical coun-

tries where globally the largest numbers of cases of dengue, lymphatic filariasis (LF), soil-trans-

mitted helminth infections, leprosy, and kala-azar are also endemic [4]. Similarly, Nigeria is

the most highly endemic country in Africa for the major NTDs, especially schistosomiasis,

soil-transmitted helminth infections, LF, onchocerciasis, and rabies. Each of these diseases has

the potential of being either introduced or reintroduced in the Middle East and North Africa

(MENA) region due to Hajj and Umrah activities.

Previously reported major Hajj-associated infectious diseases included respiratory tract

infections like seasonal influenza, meningococcal disease, lower respiratory infections due to

pneumococcus, and tuberculosis; water-borne and blood-borne infections including hepatitis

A, B, and C were discussed elsewhere [5, 6]. In this report, we focus on the major NTDs that

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OPEN ACCESS

Citation: Almutairi MM, Alsalem WS, Hassanain M,

Hotez PJ (2018) Hajj, Umrah, and the neglected

tropical diseases. PLoS Negl Trop Dis 12(8):

e0006539. https://doi.org/10.1371/journal.

pntd.0006539

Editor: Samuel V. Scarpino, Northeastern

University, UNITED STATES

Published: August 16, 2018

Copyright: © 2018 Almutairi et al. This is an open access article distributed under the terms of the

Creative Commons Attribution License, which

permits unrestricted use, distribution, and

reproduction in any medium, provided the original

author and source are credited.

Funding: The authors received no specific funding

for this work.

Competing interests: PJH is investigator and

patent holder on several vaccines in development,

including vaccines for diseases discussed in the

article.

have either been introduced into the Middle East through Hajj and Umrah pilgrimages from

tropical disease–endemic countries of Asia and Africa or where importation from Saudi Ara-

bia to other parts of the world are possible. In some cases, these diseases have now become

Fig 1. Outline map of Saudi Arabia and surrounding countries. The capital Riyadh, the two holy cities Makkah and Medina, and other

cities mentioned in this paper are shown. Original figure.

https://doi.org/10.1371/journal.pntd.0006539.g001

Table 1. Countries with the largest numbers of Hajj pilgrims (adapted from [3] and [4]).

Rank [3] Country [3] Major NTDs [4] Number of Hajj pilgrims in 2015 [3]

1 Indonesia Dengue, Lymphatic Filariasis, Soil-transmitted Helminthiases, Leprosy 168,000

2 Pakistan Dengue, Trachoma, Kala-azar, Cutaneous Leishmaniasis 143,368

3 India Dengue, Lymphatic Filariasis, Soil-transmitted Helminthiases, Leprosy, Rabies, Kala-azar, Trachoma 136,020

4 Bangladesh Dengue, Lymphatic Filariasis, Soil-transmitted Helminthiases, Leprosy, Kala-azar 101,758

5 Nigeria Schistosomiasis, Intestinal helminth infections, Lymphatic Filariasis, Onchocerciasis, Rabies 76,000

6 Egypt Schistosomiasis, Intestinal helminth infections 63,000

Total 688,146

Abbreviations: NTDs; neglected tropical diseases

https://doi.org/10.1371/journal.pntd.0006539.t001

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0006539 August 16, 2018 2 / 9

endemic in Saudi Arabia and elsewhere in the MENA region. Our report emphasizes the

recent scientific literature published within the last five years.

Arbovirus infections

Because Aedes aegypti mosquitoes are found in the western Arabian Peninsula [7], there is potential for arboviral diseases such as dengue, Zika virus infection, yellow fever, and chikun-

gunya to be introduced to Saudi Arabia through Hajj and Umrah activities. This is especially

the case when infected individuals, often from Asia, enter Saudi Arabia through Jeddah, the

major airport servicing the Hajj and Umrah (Fig 1). The first imported dengue cases from

Zanzibar to the Arabian Peninsula were reported in the 19th century, notably in Yemen in

1872 and again in 1877 [8]. It is believed that dengue may have recently emerged through an

Asian entry pathway in 1994 when dengue outbreaks were reported and found to be caused by

dengue virus-1 (DENV-1) and DENV-2 [5, 7, 9]. Subsequently, DENV-3 may have been intro-

duced in 1997 [9], with all three serotypes still circulating in western Saudi Arabia. Using full

genome and envelope (E) gene sequencing of DENV-2 strains in Saudi Arabia, it has been sug-

gested that there continues to be multiple dengue introductions, most recently from the Indian

subcontinent, most likely Pakistan, in 2014 [9, 10]. Altogether, there is a high potential that

these arboviral diseases could emerge during the Hajj and Umrah.

Based on the ease of introduction of dengue into Saudi Arabia, there are concerns that

other A. aegypti mosquito-transmitted viruses could follow during Hajj seasons. Of particular concern was the possibility of Zika virus infection emerging as a consequence of mass migra-

tions through Jeddah in 2015–2016 [11, 12], although there is no evidence for this actually

occurring [10]. Yet another concern was reports of a Chinese worker from Angola introducing

the first known case of yellow fever in China in 2016 during the large outbreak across West

Africa in that year [13, 14]. This prompted vigilance for yellow fever emerging in western

Saudi Arabia either through Hajj and Umrah pilgrimages, or from sub-Saharan Africa across

the Red Sea through multiple points of entry [13, 14]. Adding to the worries was the shortage

of yellow fever vaccine reported in that year.

Finally, Rift Valley fever (RVF, a Phlebovirus in the family Bunyaviridae) is believed to have been introduced at least twice into the MENA region from sub-Saharan Africa including entry

into Egypt from Zimbabwe in the 1970s and from Kenya into Saudi Arabia near the border

with Yemen in 2000 [15]. The Saudi Arabia–Yemen outbreak is believed to be the first and

only epizootic of RVF outside of Africa and may have emerged in part from floods due to

heavy rains in that year, which helped to promote transmission through Culex triteniorynchus and Aedes vexans arabiensis mosquitoes [15–17]. The outbreak affected approximately 40,000 animals, especially sheep and goats, with 883 human cases and 124 deaths in Saudi Arabia,

together with 1,328 human cases and 166 deaths in Yemen [17]. Intermittent diagnosis of

cases has persisted [17].

Hemorrhagic fever virus infections

Because ixodid ticks of the genus Hyalomma are indigenous to western Saudi Arabia including Makkah city, there is potential for introducing tick-borne hemorrhagic fever viruses [18]. In

1990, a Crimean-Congo hemorrhagic fever virus (CCHF) outbreak happened in Makkah

among abattoir workers [18]. The disease was introduced to the western region through the

Jeddah seaport via tick-infected imported animals [18, 19].

Another tick-borne (both Hyalomma hard ticks and Ornithodoros soft ticks) viral infection, Alkhumra hemorrhagic fever virus (AHFV), was first identified in western Saudi Arabia.

Between November and December of 1995, AHFV was isolated for the first time from blood

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0006539 August 16, 2018 3 / 9

samples of six butchers who worked for a slaughterhouse in Alkhumra (a small town near

Makkah) [20]. AHFV is considered to be one of the deadliest viral infections, with the case

fatality rate ranging between 25%–30% [20, 21]. According to a Saudi Ministry of Health data

set, 281 new cases were confirmed during 2011–2014, and all of these cases had clustered in

the Makkah and Najran regions (Fig 1) [22]. Comparative analysis between different tick-

borne flaviviruses confirmed that AHFV is most closely related to Kyasanur Forest disease

virus (KFDV), another hemorrhagic fever virus that causes hemorrhagic fever in Karnataka

State, India. Genetic distance mapping further indicates that AHFV is a subtype of KFDV, sug-

gesting that the transmission of AHFV occurred from the Indian subcontinent, possibly

through the Hajj and animal importation [21].

Because the 2014 Hajj season coincided with the Ebola outbreak in West Africa, the Saudi

authorities suspended issuing Umrah and Hajj visas for people from Guinea, Liberia, and

Sierra Leone during that year [23]. Until today, there had been no reported cases of Ebola

virus during Hajj. Continuous surveillance against Ebola remains active [24].

Other viral infection

Since its discovery in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

infected around 1,800 individuals with a 35% fatality rate. About 80% of the reported cases

occurred in Saudi Arabia [25]. The first case of MERS-CoV occurred only a few weeks before

the 2012 Hajj season. However, to date, no transmission of MERS-CoV has occurred among

Hajj or Umrah pilgrims [2]. In addition, different studies showed no evidence of MERS-CoV

transmission among returning pilgrims [2]. Given the fact that a majority of the cases hap-

pened in Saudi Arabia, MERS-CoV exportation from people leaving Saudi Arabia during the

Hajj or Umrah remains a concern.

Vector-borne protozoan infections

Saudi Arabia is ranked among the highly endemic countries of cutaneous leishmaniasis (CL).

During the last 10 years, the number of reported CL cases has dramatically dropped, with the

average reported annual prevalent cases being around 2,500 [26, 27]. Both of the major parasites

causing CL in the Middle East, Leshmania major (zoonotic species) and L. tropica (anthropono- tic species), and the vector sand flies (Phlebotomus papatasi and P. sergenti) are distributed throughout Saudi Arabia, including the two holy cities (Makkah and Medina). As a result, CL

could be potentially transmitted to other countries through Hajj and Umrah pilgrims leaving

Saudi Arabia. In fact, different reports indicate that CL may have been introduced to Asia and

Europe through Saudi Arabian visitors [28–30]. Compounding this issue is the finding that CL

is now hyperendemic in conflict regions in Syria, Iraq, and Yemen [31, 32].

Malaria previously posed a threat to Hajj and Umrah pilgrims in western Saudi Arabia.

However, decades of malaria control programs have helped to minimize these threats. For

example, between 2010 and 2015, the indigenous malaria cases remained below 100 per year.

This number increased to 272 cases in 2016. The total confirmed malaria cases in 2016 was

5,382 (indigenous and imported). The vast majority of these cases (95%) was due to importa-

tion, possibly through Hajj, workers and illegal migrants from South Asian and African

nations and Yemen, where malaria is endemic [33]. Therefore, beyond the modest levels of

autochthonous malaria transmission, Saudi Arabia faces regular importations of malaria and

its Anopheles mosquito vector, especially from highly endemic African Muslim–majority nations. Surveillance programs in place in Makkah help to limit local transmission [34, 35].

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Enteric infections

The Hajj gathering over a small area of land provides opportunities for the emergence of

enteric bacterial infections, which include antibacterial-resistant strains. For example, during

the Hajj seasons between 2011–2013, Salmonella, Shigella, and Escherichia coli accounted for the majority of the circulating enteric infections, with approximately more than one third of

these bacteria harboring β-lactamases resistance genes [36]. Active acquisitions of different resistant genes were observed among returning pilgrims, including genes resistant to the last

resort antibiotic (colistin) for Gram-negative bacteria [37]. Therefore, returning pilgrims

could facilitate dissemination of the multidrug-resistant (MDR) bacteria globally. Since MDR

bacteria are emerging worldwide, it might be expected that MDR bacteria will become an

increasing problem during coming Hajj seasons. The situation is complicated by the lack of

vaccines against most bacterial infections combined with the severe decrease in the new anti-

microbials in the clinical development pipeline.

Multiple cholera outbreaks occurred during the Hajj between 1877 and 1912. The largest

cholera outbreak occurred in 1893 with total deaths of 32,994 at the end of the Hajj season

[38]. Cholera during the Hajj was eventually brought under control through several control

measures, including quarantine, vaccination, and improvements to infrastructures for surveil-

lance and rapid detection. One concern is the current cholera epidemic in Yemen, where the

prevalence is estimated at 266 per 10,000 population. In 2016, 19,500 Yemenis obtained a visa

for the Hajj, so it is possible that cholera cases would spread into Saudi Arabia through Hajj

and Umrah pilgrimages. The finding that about 80% of individuals infected with Vibrio cho- lerae do not show symptoms and remain undetected complicates detection and surveillance efforts [39].

Disease control

The government of Saudi Arabia undertakes enormous efforts for planning the Hajj and

Umrah seasons each year through 24 different committees representing the different Saudi

sectors. The design of the annual plan is coordinated with different international agencies,

including the World Health Organization (WHO), the European Centre for Disease Preven-

tion and Control (ECDC), and the United States Centers for Disease Control and Prevention

(CDC), which provide more information about development of outbreaks and emerging dis-

eases including NTDs. Based on these combined efforts, the Saudi Ministry of Health issues

recommendations for the required vaccinations and other preventive measures.

The ambitious Saudi Arabia’s Vision 2030, “@SaudiVision2030,” (a methodology and road-

map for economic and developmental transformation in Saudi Arabia) includes programs that

introduce major transformation to the different sectors and services within the country. A key

strategic program is ensuring opportunities to expand safe Hajj and Umrah pilgrimages [40].

To achieve this goal, the Saudi government recently started expansion plans for the two holy

mosques in Makkah and Medina as well as efforts to increase the capacities of the international

and regional airports in and around the two holy cities. In 2015, the number of Umrah pil-

grims was 8 million, but this number is expected to reach 18 and 30 million by 2020 and 2030,

respectively.

As a result of the increase in the pilgrims to Saudi Arabia, the risk of NTDs is magnified.

Therefore, the future plans for Umrah and Hajj expansion also include strengthening the health-

care system and constructing a national plan to deal with potential public health threats. The

Saudi government’s health sector expansion also includes research and development (R&D)

capacity building. For example, Saudi Arabia intends to build a national center for vaccine and

biologic research and development within King Saud University (KSU) in Riyadh. KSU is a

PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0006539 August 16, 2018 5 / 9

leading university in healthcare research, and in order to support establishing this center, it

signed an agreement with the Texas Children’s Hospital Center for Vaccine Development, foc-

using on education and training and to support the transfer of technology to the Kingdom of

Saudi Arabia. This collaboration will help to train Saudi scientists at various steps of vaccine

development and help to establish a parallel vaccine facility in Saudi Arabia. The ultimate goal

for the Saudi’s national center for vaccine and biologic research and development is to help in

the research and development of vaccine candidates against local and regional infectious dis-

eases, including major NTDs in the region. Furthermore, the Saudi Ministry of Energy, Industry,

and Mineral Resources is sponsoring a new Saudi Vaccine and Biopharmaceutical Center fun-

ded by the King Abdulaziz City for Science and Technology (KACST, the major funding agency

for R&D in Saudi) and operated by SaudiVax and PnuVax, applying the concept of govern-

ment-owned, contractor-operated model (GOCO). The center will have the capacity to scale up

cell-based vaccines up to 2,000 L under good manufacturing practice (GMP) guidelines with

approval from the Saudi Food and Drug Authority (SFDA). The idea of the center is to support

moving early discoveries from the bench to the market, especially those with low global market

value and so week incentives for large multinationals to support. Finally, the Saudi government

has formed a thinktank with representatives from the different groups mentioned above and

from the policy-making side that is called the “Saudi Vaccine Alliance.” This thinktank is used

to address matters related to combating new issues and to expand on the Saudi reach to the

international scientific community.

Similar efforts will be required to expand disease diagnostic capacity. In that context, the

Saudi Ministry of Health has recently mandated the expansion of the National Health Labora-

tory (NHL) located north of Riyadh, with emphasis on increased capacity and scope for its ref-

erence diagnostic labs, including three core laboratories: infectious diseases, genetic diseases,

and molecular biology systems. The NHL aims to support the Saudi’s strategic plans by achiev-

ing high standards in scientific research, diagnosis, and disease prevention. The NHL expan-

sion includes the establishment of a new Center for Neglected Tropical Diseases.

Indeed, during the coming years, we can continue to expect a large influx of pilgrims to

Saudi Arabia, especially from countries known to be endemic for NTDs. Therefore, there is an

urgent need for development of more comprehensive surveillance programs and data collec-

tion not only during the Hajj but also around the year to account for Umrah pilgrims. Such

programs could monitor for any possible outbreaks for all NTDs highlighted above, with an

emphasis on countries with the highest number of pilgrims coming from NTD-endemic

nations. In addition, surveillance monitoring will continue to include Hajj and Umrah pil-

grims leaving Saudi Arabia and traveling globally. Collectively, these data will enable the pol-

icymakers to make informed decisions to control and prevent NTDs in the Middle East and

also in all of the Muslim-majority nations comprising the Organization of the Islamic Confer-

ence (OIC).

In parallel, many of the NTDs highlighted above are transmitted by insects and ticks, which

are now widespread in the western region of Saudi Arabia. Therefore, intensified vector man-

agement and control will represent a critical component of health sector planning for the Hajj

and Umrah. Toward that goal, the Saudi Ministry of Health through the Center for NTDs will

develop programs to focus on vector controls and surveillances.

In summary, mass gatherings may facilitate the emerging of NTDs just as they do other dis-

eases of epidemic or pandemic potential. Since the Hajj and Umrah represent international

gatherings, collaboration at multiple levels is required, including expanded surveillance and

intensified vector management and control, increased reference laboratory diagnostic testing,

and R&D for both new diagnostics and vaccines. Through its strategic planning, the Ministry

of Health and its research university and institute partners are committed to undertaking a

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multidimensional approach to disease threats in the Kingdom of Saudi Arabia, the MENA

region, and across the OIC nations.

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