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Published Date: 2017-07-16 12:03:46
Subject: PRO/EDR> Typhoid fever - Pakistan: (SD) multidrug resistance, RFI
Archive Number: 20170716.5178355

A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Sun 16 Jul 2017
Source: Geo television [edited]

More than 250 children have been affected by multi-drug resistant typhoid (MDR) typhoid in Hyderabad, said Dr Farah Qamar, the Assistant Professor of Pediatric at the Aga Khan University Hospital.

Qamar, who conducted a survey in different areas of Hyderabad and Karachi, warns that it is "typhoid at its worst," adding that the 2 cities are seeing the biggest outbreak of MDR typhoid.

In Karachi, 15 children have been affected by the outbreak, Dr Qamar added. The worst affected areas of Karachi, where an antimicrobial-resistant strain of typhoid is circulating, were found to be Lyari, North Karachi, Gulshan-e-Hadeed, Gulistan-e-Jauhar, Malir and Ibrahim Haydri.

Areas in Hyderabad affected by the outbreak include Bhittai Colony, Qasimabad, and Wehdat colony, where the affected include children under the age of 2 to 5 years.

According to Dr Qamar, the primary reason for the outbreak is un-chlorinated water, contaminated water, and poor sanitation and sewerage conditions, which have contributed to an increase in MDR germs in the environment. Another issue highlighted during her survey is the condition of all 4 water treatment plants in Hyderabad district, which are non-functional and are supplying contaminated water to the residents.

As the cases are hard to treat, Dr Qamar stressed the importance of managing the cases to prevent outbreaks. The situation has worsened since November 2016, but no concrete actions have been taken by the authorities. Dr Mohammad Taufeeq, Director Health of Karachi, confirmed the presence of MDR typhoid and said that vaccinations with the help of Child Survival Program have been started in Lyari, Ibrahim Hyderi and Gadap town.

Dr M.N Lal, Program Director of Child Survival in Sindh, suggested that for MDR typhoid prevention, people need to ensure avoiding unhygienic food and water, ensuring tap water is chlorinated, ensuring personal hygiene, and drinking boiled water.

Prevention can be done by vaccination with the Typbar vaccine, which can be given to children aged more than 2 years, adds Dr Qamar.

In addition, awareness about the overuse of drugs is being discussed with local physicians. "We need to limit the inappropriate use of antimicrobials or face more outbreaks," says Dr Qamar. "Globally, drug-resistant typhoid is spreading across Africa and Asia, and we need to work together to develop methods to identify new cases, clinically evaluate and treat those who are affected, and find prevention and control measures."

Lack of chlorination of water in Karachi is also a major culprit. According to Deputy Secretary Health Dr Zafar Mehdi, the primary responsibility for chlorination of water lies with Karachi Water and Sewerage Board (KWSB). Health experts say Pakistan is signatory to the UN sustainable development goals and must carry out a mandatory effort to control typhoid disease.

Typhoid is one of the common causes of death in children in South Asia, and a lack of awareness and the abysmal situation of basic utilities affect millions of children every year. Health experts urge the government to take concrete steps to save future generations from contracting the disease by providing clean and safe water and repairing and separating the sewerage lines from water lines.

Communicated by:
ProMED-mail Rapporteur Kunihiko Iizuka

[ProMED thanks Kunihiko Iizuka for this posting.

This outbreak may well be caused by _S._ Typhi, H58, defined based on single nucleotide polymorphisms frequently referred to as SNPs (pronounced "snips"), which has been accounting for a significant amount of morbidity and mortality, which may be based on its increasingly antimicrobial resistance. ProMED would appreciate more information regarding the outbreak strain and its antimicrobial sensitivity pattern(s).

The following is abstracted from the introduction of the article, Wong VK, Baker S, Pickard DJ, et al: Phylogeographical analysis of the dominant multidrug-resistant H58 clade of _Salmonella_ Typhi identifies inter- and intracontinental transmission events. Nature Genetics. 2015;47:632-639 with the citations removed:

"_S._ Typhi, the primary global cause of human typhoid (enteric fever), is a monophyletic serovar of _S. enterica_. Unlike many Salmonella, _S. Typhi_ are highly restricted to infection of humans and are associated with systemic infection, prolonged fever and an asymptomatic carrier state. Typhoid is still a common disease in many regions of the world with poor infrastructure and limited economic development and is also a risk for travelers who visit such regions. It is estimated that 20-30 million cases of typhoid occur annually, although deaths are less frequently reported than before the availability of effective antimicrobials.

In addition to improvements in access to clean water and sanitation, typhoid can potentially be controlled by other interventions such as vaccination and antimicrobial therapy. Chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole were traditional 1st-line drugs commonly used to treat acute typhoid, and these agents continue to be used in areas of the world where _S._ Typhi are deemed susceptible. However, since the 1970s, _S._ Typhi have emerged that display multidrug resistance, defined as resistance to the above antimicrobials, compromising treatment. Since the 1990s, alternative treatment options have included fluoroquinolones, 3rd-generation cephalosporins (such as ceftriaxone) and the azalide azithromycin. The early emergence of MDR _S._ Typhi was driven in large part by the acquisition of IncHI1 plasmids carrying antibiotic resistance genes and, more recently, by chromosomal mutations associated with resistance to fluoroquinolones, and MDR strains have been reported across Asia and Africa.

Phylogenetic analysis, initially based on subgenomic DNA sequences but later on whole-genome DNA sequences, showed that the global _S._ Typhi population is highly clonal and likely originated from a common ancestor that moved into the human population several thousand years ago. It also indicated that the population is relatively small and that recombination between _S._ Typhi and other salmonellae is rare. Simple SNP-based typing schemes have been developed that stratify the _S._ Typhi population into haplotypes, and these schemes are now used to unequivocally map new isolates to the phylogeny. Notably, this approach identified a single emerging, highly clonal MDR haplotype of _S._ Typhi, H58, which is being reported with increasing frequency from many countries in Africa and Asia. Within the H58 lineage, IncHI1 MDR plasmids of the restricted subtype PST6 and chromosomal point mutations conferring quinolone resistance are common." - Mod.LL

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See Also

Typhoid fever - Zambia: (LS) 20170524.5059531
Typhoid fever - New Zealand (04): (MW) 20170524.5058851
Typhoid fever - Syria: (HL) 20170523.5057372
Typhoid fever - Kenya: H58 haplotype, antimicrobial resistance 20170430.5005152
Typhoid fever - Tonga 20170414.4971570
Typhoid fever - New Zealand (03): (AU) church community 20170413.4969569
Typhoid fever - New Zealand (02): (AU) church community 20170405.4947714
Typhoid fever - New Zealand: (AU) RFI 20170403.4943251
Typhoid fever - Zimbabwe (02): (HA) 20170402.4942851
Typhoid fever - Zimbabwe: (Harare) 20170107.4749025
Typhoid fever - USA: (CO) restaurant cluster, 2015 20160624.4307017
Typhoid fever - Zimbabwe: (Harare) 20160318.4103720
Typhoid fever - USA: (CO) restaurant cluster 20151107.3774978
Typhoid fever - Syria (03): (DI) refugee camp 20150928.3670433
Typhoid fever - Syria (02): (DI) susp., refugee camp 20150903.3622700
Typhoid - Syria: (DI) refugee camp 20150821.3591694
Typhoid fever - Nepal: (SP) post-earthquake 20150726.3528925
Typhoid fever - Africa, Asia: multidrug resistant 20150512.3357675
Typhoid fever - Fiji (02): (NO) commentary 20150123.3114013
Typhoid fever - Fiji: (NO) 20150122.3111081

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