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Tetanus in adult males, Bugando Medical Centre, United Republic of Tanzania

Abstract Problem In the United Republic of Tanzania, the incidence of non-neonatal circumcision-related tetanus is probably underreported. Approach We analysed charts and extracted information on outcome and wound location for non-neonatal cases of tetanus admitted to the intensive care unit of Bugando Medical Centre between 2001 and 2016. Local setting Bugando Medical Centre, which is one of four teaching referral hospitals in the United Republic of Tanzania, has a 13-bed intensive care unit that manages all admitted patients with tetanus. Within the United Republic of Tanzania, formal programmes of tetanus immunization are targeted at infants or women. Relevant changes From our inpatient logs, we identified six patients with non-neonatal tetanus among male patients with a recent history of circumcision. Only one of these patients had been circumcised within a subnational programme of voluntary medical male circumcision. The other five had been circumcised outside of the programme – e.g. at small rural dispensaries or by a traditional provider with no formal medical training. The six patients were aged 11–55 years and five (83%) of them died in hospital – all of overwhelming sepsis. Lessons learnt Within the Tanzanian programme of voluntary medical male circumcision, education on wound hygiene probably helps to reduce the incidence of non-neonatal circumcision-related tetanus. The corresponding incidence among the boys and men who are circumcised beyond this subnational programme is probably higher. The training of all circumcision providers in wound care and a vaccination programme to ensure that male Tanzanians receive tetanus immunization post-infancy are recommended.


Introduction
By 2012, 14 countries in eastern and southern Africa -including the United Republic of Tanzania -had been prioritized for the scale-up of voluntary medical male circumcision. 1 The goal of the scale-up was to reduce the transmission of human immunodeficiency virus (HIV) by circumcising over 35 million males in the priority countries by 2020. 1 Only 13 cases of tetanus -one of which was Tanzanian, were attributed to the voluntary medical male circumcisions, that were performed in the 14 priority countries between 2012 and 2016. 2 Since 2009, the United Republic of Tanzania has had a subnational programme of voluntary medical male circumcision that covers the Lake Zone in the north of the country. Between 2009 and 2015, this programme, which has received support from the United States Agency for International Development, the United States President's Emergency Plan for AIDS Relief and other international donors, provided 497 259 circumcisions. 3 Based on our clinical experience working in the intensive care unit at a Tanzanian referral hospital, we believed that non-neonatal male circumcision-related tetanus was being underreported in the United Republic of Tanzania. We therefore decided to conduct a detailed investigation of the patients with non-neonatal tetanus admitted to our hospital between 2001 and 2016, to see how many, if any, were related to recent circumcision.

Local setting
Our study was conducted in the United Republic of Tanzania. We investigated tetanus patients admitted to the Bugando Medical Centre, which is one of just four referral teaching hos-pitals in the country. The Bugando Medical Centre is located in the city of Mwanza and serves 15 million people, who live in the Lake Zone. Throughout our study period, the Centre had a 13-bed intensive care unit that included seven ventilators.
The United Republic of Tanzania has been covered by the Expanded Programme on Immunization since 1975. 4 Although the programme's general coverage of its target Tanzanian population was estimated to be about 50% in the early 1980s, 4 tetanus vaccine coverage among Tanzanian children younger than one year was estimated to have risen to 87.8% by 2010. 5 The Tanzanian programme of tetanus vaccination is targeted at children younger than one year and women of childbearing age, i.e. women aged 14-49 years. In 2008, according to the Tanzanian Ministry of Health and Social Welfare, 80% of pregnant women received at least one dose of tetanus toxoid and 56% of women received at least two doses. 6 There is no system in place to ensure that Tanzanian males receive any tetanus toxoid after their infancy, despite international recommendations for repeat tetanus vaccination every 10 years. 7

Approach
Patients admitted to Bugando Medical Centre are recorded prospectively in log books, together with their diagnoses and dates of admission. We investigated all patients admitted with a diagnosis of non-neonatal tetanus to Bugando Medical Centre's intensive care unit between 1 May 2001 and 31 July 2016. Tetanus was diagnosed on clinical findings of rigidity, spasms and or trismus. All patients were managed in accordance with a standardized hospital protocol. Medical records were only available for patients admitted after 2008. For these patients,

Relevant changes
We identified 280 patients with nonneonatal tetanus who were admitted to Bugando Medical Centre's intensive care unit during our study period. These patients, of whom 241 (86.1%) were male and 141 (50.4%) died while admitted, had a median age of 30 years (IQR: 19-46). The median age of the 139 survivors was significantly lower than that of the 141 fatal cases of tetanus (27.0 vs 36.5 years; P < 0.001).
We located medical notes for 162 of the 197 patients with non-neonatal tetanus admitted after 2008. Of the patients for whom medical notes were available, 159 (98.1%) had a recorded wound anywhere, 51 (31.4%) had a recorded wound on a leg, 46 (28.4%) a recorded wound on a foot and 22 (13.6%) had a recorded wound on a hand. Six (3.7%) of these patients were males who had a recent history of circumcision without, apparently, any other recent wound ( Table 1). Five of these patients had circumcisions performed outside of the local subnational programme of voluntary medical male circumcision, i.e. at small rural dispensaries (2 men), in a traditional ceremony where the circumcision had been performed by traditional provider with no formal medical training (1 man) or in another, unspecified, location (2 men). The six patients identified as nonneonatal cases of circumcision-related tetanus were aged 11-55 years (mean: 29.8 years). Their first symptoms had been noticed one to two weeks after their circumcisions and they spent 1-22 days (mean: 8.8 days) in the intensive care unit before they died of overwhelming sepsis (5 men) or was discharged (1 man). Five of the six patients, all of whom died in the hospital, required invasive mechanical ventilation. Although the level of mortality among the patients with circumcision-related tetanus (5/6; 83.3%) was higher than that among the other patients with non-neonatal tetanus admitted after 2008 (99/191; 51.8%), the difference was not statistically significant (P = 0.09).
Although the patient who developed tetanus after being circumcised within the programme of voluntary medical male circumcision was known to be HIV-infected, we could not find any information indicating whether he was using antiretroviral therapy. No information about other potential risk factors for post-circumcision tetanuse.g. the application of cow dung to the wound 8 , was available.

Lessons learnt
At one of the four Tanzanian referral hospitals, we detected six patients with circumcision-related non-neonatal tetanus over a seven-year period. Only one of those six patients had been cir-cumcised within the local subnational programme of voluntary medical male circumcision and, in consequence, formally reported as an adverse event within the programme. 2 Good wound care is essential for the prevention of infection post-circumcision. 9 It seems likely that the incidence of tetanus within any formal programme of voluntary medical male circumcision is generally low because teaching on safe wound care accompanies most, if not all, such programmes. Our data highlight the need for a national policy that ensures that smaller dispensaries and other circumcision providers receive similar teaching on wound care. By inviting traditional providers to participate in training programmes, their knowledge, skills and willingness to engage with the more formal health services could be improved. 10,11 The development and use of a formal protocol for the management of wound care, which has been shown to reduce wound infections in remote African settings, 12 may also be beneficial in reducing tetanus infection after circumcision.
We support recent calls to integrate tetanus vaccination with adult male circumcision, as a way of boosting immune status in men. [13][14][15] Formalization of tetanus vaccination programmes and establishment of tetanus as a notifiable disease have been associated with global declines in the incidence of tetanus since the 1940s. 14 In the United States, for example, implementation of these two strategies appears to have led to a reduction in the annual incidence of tetanus from 500-600 patients in the 1940s to 25 in 2014. 14 In the United Republic of Tanzania, where tetanus reporting is not mandatory, only two patients with non-neonatal tetanus were reported in 2014. 14 The results of our  15 and only 24% (24/102) of 102 tetanus patients at the Bugando Medical Centre reported previous immunization against the disease. 13 Implementation of a robust immunization programme against tetanus, ideally coupled with mandatory tetanus reporting, could be very beneficial in the United Republic of Tanzania and should be a priority.
Our study had several limitations. First, we had no access to the medical records of patients admitted before 2009. Second, the patients we investigated are unlikely to be nationally representative because Bugando Medical Centre is only accessible to those who are able to pay for transport and treatment and well enough to travel to reach the hospital.
It therefore seems likely that we missed many patients with tetanus that occurred, during our study period, within the catchment area of Bugando Medical Centre. Future prospective studies that include both regional and district hospitals are urgently needed.
In conclusion, we believe that the teaching of wound hygiene after circumcision and administration of tetanus vaccine at the time of adult circumcision have the potential to prevent both morbidity and mortality in young Tanzanian men (Box 1). ■

Acknowledgements
We thank the staff working in the intensive care unit and medical records department at Bugando Medical Centre.   Tanzanian programme of voluntary medical male circumcision, education on wound hygiene probably helps to reduce the incidence of non-neonatal circumcisionrelated tetanus. • The corresponding incidence of circumcision-related tetanus among the boys and men who are circumcised beyond this subnational programme is probably higher. • The training of all circumcision providers in wound care and a vaccination programme to ensure that male Tanzanians receive tetanus immunization after infancy would probably be very beneficial.
Lecciones aprendidas Dentro del programa de Tanzania para la circuncisión masculina voluntaria médica, probablemente la educación sobre la higiene de las heridas ayude a reducir la incidencia del tétanos relacionado con la circuncisión no neonatal. Es probable que la incidencia correspondiente entre los niños y hombres circuncidados fuera de este programa subnacional sea mayor. Se recomienda la formación de todos los proveedores de circuncisión en el cuidado de heridas y un programa de vacunación para asegurar que los varones de Tanzania sean vacunados contra el tétanos después de la infancia.