During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic

Haselbeck, Andrea

Im, Justin

Jeon, Hyon Jin

Kang, Sophie SY

Marks, Florian

Rakotozandrindrainy, Raphaël

Sugimoto, Jonathan

Emerging Infectious Diseases

English

PubMed

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020–July 2020), compared with 13 perforations during the previous 41 months (August 2016–January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic

Hyon Jin Jeon

Florian Marks

Jonathan Sugimoto

Justin Im

Sophie S.Y. Kang

Andrea Haselbeck

Raphaël Rakotozandrindrainy

Directory of Open Access Journals

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19–Associated Delays in Seeking Care, Madagascar

Apollo (Cambridge)

In an effort to understand the health impacts of en-demic typhoid, the Severe Typhoid Fever Surveil-lance in Africa Program (SETA) detects and records cases of surgically confi rmed intestinal perforations, a relatively rare but severe complication of Salmonella enterica serovar Typhi infection (1). Since the begin-ning of the coronavirus disease (COVID-19) global pandemic in early 2020, SETA surveillance has found an alarming increase in surgically confi rmed intesti-nal perforations cases in Madagascar. This increase, which does not correlate with an increase in blood culture–confi rmed typhoid cases found through SETA surveillance, may insinuate the serious effects on healthcare-seeking behavior and healthcare quality that the COVID-19 pandemic has had in the country.Typhoid intestinal perforation is a severe com-plication of untreated or mismanaged infection that disproportionately affects low-income countries (2). Delay in diagnosis and proper antibiotic treatment of typhoid is frequently cited as a major factor contrib-uting to typhoid intestinal perforation incidence and associated deaths (3–6). As such, increases in intes-tinal perforation cases may suggest deterioration in the quality of healthcare or changes in the healthcare-seeking behavior of the community.SETA sentinel sites represent both primary and tertiary healthcare facilities, where all incoming pa-tients are screened for febrile illness, clinically sus-pected typhoid, and gastrointestinal perforations. Once a patient is enrolled in the study, cultures of their blood, stool, and (in the case of surgery) tissue are used to detect Salmonella Typhi and other bacte-remia. Over a 4-year period of SETA observation, we detected a marked increase in the rate of surgically confi rmed typhoid intestinal perforations after the onset of the COVID-19 pandemic in early 2020 (Fig-ure, panel A).SETA Madagascar enrolled case-patients with suspected typhoid intestinal perforations in the town of Imerintsiatosika, 43 km from the capital city of Antananarivo, as well as case-patients from tertiary care facilities in Antananarivo (1) (Figure). Clinical and demographic data were systematically collected from enrolled participants at entry into the study. We observed participants daily until their hospital dis-charge. We detected a total of 26 intestinal perforation cases of any etiology during August 2016–September 2020. The mean age of the patients was 28.5 years (SD + 19.1 years); men and boys accounted for 69% of the total patients. Of the 26 patients with perforation, 9 died and 17 were discharged. The overall case-fatality rate was 50% among women and girls and 28% among men and boys. Of note, all 4 deaths among women and girls occurred during the prepandemic period, and all 5 deaths among men and boys occurred during the Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19–Associated Delays in Seeking Care, MadagascarHyon	Jin	Jeon,1	Florian	Marks,1	Jonathan	Sugimoto,	Justin	Im,	Sophie	S.Y.	Kang,	Andrea	Haselbeck,1	Raphael	Rakotozandrindrainy1	 Emerging	Infectious	Diseases	•	www.cdc.gov/eid	•	Vol.	27,	No.	12,	December	2021	 3163Author	affi		liations:	University	of	Cambridge	School	of	Clinical	Medicine,	Cambridge	Biomedical	Campus,	Cambridge,	UK	(H.J.	Jeon,	F.	Marks);	International	Vaccine	Institute,	Seoul,	South	Korea	(H.J.	Jeon,	F.	Marks,	J.	Sugimoto,	J.	Im,	S.Y.	Kang,	A.	Haselbeck,);	University	of	Antananarivo,	Antananarivo,	Madagascar	(F.	Marks,	R.	Rakotozandrindrainy)DOI:	https://doi.org/10.3201/eid2712.210516 1These	authors	contributed	equally	to	this	article.During	the	coronavirus	disease	pandemic,	we	observed	a	6.4-fold	 increase	 in	 typhoid	 intestinal	 perforation	 inci-dence	 in	 Antananarivo,	 Madagascar.	 Thirteen	 perfora-tions	and	occurred	within	6	months	(February	2020–July	2020)	compared	with	13	perforations	during	the	previous	41	months	 (August	 2016–January	 2020).	 The	 increase	may	be	attributable	to	delayed	healthcare	seeking	during	the	pandemic.DISPATCHESpandemic period. During August 1, 2016–January 31, 2020, the pre–COVID-19 pandemic period, 13 perfora-tions (2.1/100,000 person-years of observation [PYO]) and 4 deaths (0.6/100,000 PYO) occurred. These inci-dence rates contrast with the remainder of 2020, the COVID-19 pandemic period, during which 13 perfo-rations (13.2/100,000 PYO) and 5 deaths (5.1/100,000 PYO) occurred. This change represents a 6.4-fold (95% CI 3.0–13.7-fold) increase in the incidence of intestinal perforations during the COVID-19 pandemic period (p<0.05). Although we noted no statistically signifi-cant difference in mean age of onset for intestinal per-foration patients detected before versus after the onset of the pandemic (30 vs. 27 years; p = 0.75 by t-test), intestinal perforation patients identified during the pandemic seem more likely to be middle-aged (20–50 years of age) (Figure, panel A).We suspect that the immediate increase in inci-dent intestinal perforations observed since February 2020 may be an externality of delayed treatment for mild typhoid fever because of changes in health-care-seeking behavior, healthcare quality, or both during the initial COVID-19 pandemic outbreak. However, COVID-19 investigations to date indicate that COVID-19 can affect various organs, includ-ing the gastrointestinal tract; hence, the possibility of SARS-CoV-2 having a direct effect on the risk for perforations cannot be ruled out at this stage and warrants further research.As of Oct 19, 2021, a total of 42,898 COVID-19 cases and 958 COVID-19–related deaths had been re-ported in Madagascar (7). Well before the first 3 cases of COVID-19 were reported in-country on March 20, 2020, media coverage of the global pandemic was sub-stantial (8,9). Like the rest of the international com-munity, Madagascar watched with collective anxiety and apprehension as the novel coronavirus outbreak unfolded. Although the surge of reported perforation cases predates regional lockdowns, which were first imposed in July 2020 (10), we cannot rule out ad hoc closures of healthcare centers affecting the commu-nity’s ability to seek regular care in addition to the unknowns of potential social stigma that raises bar-riers to the already low levels of healthcare-seeking observed during nonpandemic conditions in the com-munity (11,12).Before future in-depth qualitative research can provide a comprehensive picture of healthcare in Madagascar during the COVID-19 pandemic, SETA screening records may provide the first hint at a dis-ruption of individual healthcare-seeking behavior as shown by a reduction in the number of overall pa-tient hospital visitations beginning in January 2020 (Figure, panel B). SETA records all patients who visit any of the sentinel health centers for any concern and screens those patients for study eligibility; conse-quently, SETA screening numbers can be understood as a proxy for hospital visitation numbers.3164	 Emerging	Infectious	Diseases	•	www.cdc.gov/eid	•	Vol.	27,	No.	12,	December	2021Figure.	Typhoid	intestinal	perforation	cases	and	number	of	patients	screened	in	hospitals	participating	in	the	Severe	Typhoid	Fever	Surveillance	in	Africa	Program	(SETA),	Madagascar,	July	2016–September	2020.	A)	Intestinal	perforation	cases	recorded	by	SETA	at	3	hospitals,	by	age	of	patient	and	date	of	hospitalization.	B)	Number	of	patients	screened	monthly	by	SETA	at	Hospital	Joseph	Ravoahangy	Andrianavalona,	the	largest	hospital	in	the	capital	city	of	Antananarivo,	and	its	tertiary	care	center,	and	at	the	Centres	Santé	de	Bases	II,	a	primary	care	facility	in	the	town	of	Imerintsiatosika	in	the	rural	region	west	of	Antananarivo.	Vertical	purple	lines	indicate	date	first	case	of	COVID-19	reported	in	Africa.	CSB-II,	Centres	Santé	de	Bases	II;	HJRA,	Hospital	Joseph	Ravoahangy	Andrianavalona.Typhoid	Intestinal	Perforations,	MadagascarThe COVID-19 pandemic is likely having broad impacts on other preventable diseases in an already struggling healthcare system; widespread availabil-ity of COVID-19 vaccines in Madagascar is expected only in 2023 (13). The observed increase in illness and deaths from treatable diseases and disruption of routine primary care should not be neglected (14,15). Although the SETA program has only investigated intestinal perforations in the capital city, delayed healthcare-seeking might be an even larger prob-lem in more remote areas of the country. The public health community must remain vigilant about main-taining routine healthcare services and ensuring that healthcare facilities are safe and usable. In par-ticular, public trust in the healthcare system amidst the pandemic is essential for encouraging persons with potentially life-threatening conditions to seek healthcare.The SETA Program is funded by the Bill and Melinda Gates Foundation (grant no. OPP1127988).About the AuthorMs. Jeon is Project Manager in the Department of  Medicine at the University of Cambridge and Senior  Program Administrator at the International Vaccine  Institute. Her research interests include disease  surveillance for bacterial and viral infections. Ms. Jeon is currently working on her PhD investigating field site analysis of invasive Salmonellosis in sub-Saharan Africa. Dr. Marks is the Deputy Director General at the  International Vaccine Institute, Principal Research  Associate at the Department of Medicine, University of Cambridge and holds an appointment at the University  of Antananarivo. His research interest includes  vaccine-preventable diseases epidemiology and vaccine impact assessments. References  1. Park SE, Toy T, Cruz Espinoza LM, Panzner U, Mogeni OD, Im J, et al. The Severe Typhoid Fever in Africa Program: study design and methodology to assess disease severity, host immunity, and carriage associated with invasive  salmonellosis. Clin Infect Dis. 2019;69(Suppl 6):S422–34. https://doi.org/10.1093/cid/ciz715  2. Contini S. Typhoid intestinal perforation in developing countries: still unavoidable deaths? World J Gastroenterol. 2017;23:1925–31. https://doi.org/10.3748/wjg.v23.i11.1925  3. Ameh EA. Typhoid ileal perforation in children: a scourge in developing countries. Ann Trop Paediatr. 1999;19:267–72. https://doi.org/10.1080/02724939992356  4. Ekenze SO, Ikefuna AN. Typhoid intestinal perforation  under 5 years of age. Ann Trop Paediatr. 2008;28:53–8. https://doi.org/10.1179/146532808X270680  5. Sümer A, Kemik O, Dülger AC, Olmez A, Hasirci I, Kişli E,  et al. Outcome of surgical treatment of intestinal  perforation in typhoid fever. World J Gastroenterol. 2010;16:4164–8. https://doi.org/10.3748/wjg.v16.i33.4164  6. Bitar R, Tarpley J. Intestinal perforation in typhoid fever: a historical and state-of-the-art review. Rev Infect Dis. 1985;7:257–71. https://doi.org/10.1093/clinids/7.2.257  7. Worldometer. Madagascar coronavirus cases: 42,898; deaths: 958 [cited 2021 Oct 19]. https://www.worldometers.info/coronavirus/country/madagascar  8. Rasolo F. Suspension temporaire des vols Antananarivo-Guangzhou. Madagascar Tribune. 2021 Jan 31 [cited 2021 Oct 19]. https://www.madagascar-tribune.com/Suspension-temporaire-des-vols-Antananarivo-Guangzhou.html   9. Madagascar: country confirms first cases of COVID-19 March 20 /update 3. GardaWorld. 2020 Mar 20 [cited 2021 Oct 19]. https://www.garda.com/crisis24/news-alerts/325126/madagascar-country-confirms-first-cases-of-covid-19-march-20-update-3 10. Anadolu Agency. Madagascar imposes lockdown amid  rise in COVID-19 cases. 2020 Jul 6 [cited 2021Oct 19]. https://www.aa.com.tr/en/africa/madagascar-imposes-lockdown-amid-rise-in-covid-19-cases/190094011. Logie CH. Lessons learned from HIV can inform our ap-proach to COVID-19 stigma. J Int AIDS Soc. 2020;23:e25504. https://doi.org/10.1002/jia2.2550412. World Health Organization Regional Office for Africa.  Combattre la peur et la stigmatisation liées à la COVID-19. 2020 Jul 23 [cited 2021 Oct 19]. https://www.afro.who.int/fr/news/combattre-la-peur-et-la-stigmatisation-liees-la-covid-19 13. More than 85 poor countries will not have widespread access to coronavirus vaccines before 2023. Economist Intelligence Unit. 2021 Jan 27 [cited 2021 Oct 19]. https://www.eiu.com/ n/85-poor-countries-will-not-have-access-to-coronavirus-vaccines14. Ansumana R, Sankoh O, Zumla A. Effects of disruption from COVID-19 on antimalarial strategies. Nat Med. 2020;26:1334–6. https://doi.org/10.1038/s41591-020-1047-515. Barach P, Fisher SD, Adams MJ, Burstein GR, Brophy PD, Kuo DZ, et al. Disruption of healthcare: will the COVID pandemic worsen non-COVID outcomes and disease  outbreaks? Prog Pediatr Cardiol. 2020;59:101254.  https://doi.org/10.1016/j.ppedcard.2020.101254Address for correspondence: Florian Marks, International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea; email: fmarks@ivi.int	 Emerging	Infectious	Diseases	•	www.cdc.gov/eid	•	Vol.	27,	No.	12,	December	2021	 3165

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

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