Outbreak Investigation of Monkeypox in Akwa Ibom State : A Matched Case Control Study 14 th-24 th October 2019

Background: Monkeypox (MPX) is a viral zoonoses characterized by pustular rashes similar to smallpox. It is endemic in the Democratic Republic of Congo and West Africa. The outbreak of MPX was first reported outside Africa in 2003 following horizontal infection of Prairie dogs by imported African rodents. Two distinct clades are known, the Central (more severe) and the West African clade (Mild). In Nigeria, the first confirmed case of MPX was in a 4-year old child in 1971. This was followed by a lull of 39 years. Since September 2017, sporadic outbreaks have been reported in 17 states across Nigeria. As at week 36 of 2019, Akwa Ibom reported ten suspected cases with one lab-confirmed.


INTRODUCTION
Monkeypox (MPX) is a zoonotic viral disease (Beer & Id, 2019;Heymann, Szczeniowski, & Esteves, 1998;Yinka-Ogunleye et al., 2018). It was first identified in 1958 among colonies of monkeys kept for research purposes and its natural reservoirs are presently unknown (CDC, 2019). Wild rodents and primate monkeys are believed to play a role in its transmission (CDC, 2019;WHO, 2018). Two distinct genetic groups of Monkeypox are known; the central and the West Africa group (clade) where the former is responsible for severe morbidity (Beer & Id, 2019;CDC, 2019). Clinical symptoms seen in suspected cases include fever, headache, muscle pains, including lesions such as pustular rashes identical to smallpox except for marked lymphadenopathy in the former (Beer & Id, 2019). Smallpox was eradicated in 1980 since then Monkeypox has grown to global recognition with chickenpox as a differential (Heymann et al., 1998).
Human infection with MPX was first reported in the Democratic Republic of Congo in 1970(CDC, 2019Sejvar et al., 2004), then in West Africa where the disease is endemic. Studies on MPX zoonoses conducted between 1970-1980 concluded that Monkeypox outbreaks are sporadic in nature with few human to human infection not exceeding two generations and case fatalities between 1-10% (Heymann et al., 1998;WHO, 2018). However, person to person spread of Monkeypox has been reported three times outside Africa (USA in 2003, UK andIsrael in 2018) (CDC, 2019). After over 39 years lull in Monkeypox outbreak in Nigeria, the Nigerian Center for Disease Control (NCDC) was notified of a suspected case of Monkeypox on September 22, 2017(NCDC, 2017Yinka-Ogunleye et al., 2018), which was later confirmed to be positive for MPX (NCDC, 2017). Genetic sequencing suggested multiple sources MPX virus into human population (NCDCl, 2019).
Ever since the 2017 case, Nigeria continued to report sporadic cases between January 2019 and September 2019 where 81 suspected cases were reported of which 39 cases were confirmed across nine States namely Bayelsa, Lagos, Delta, Rivers, Akwa Ibom, Enugu, Anambra, Cross River, and Oyo. 59% of the confirmed cases were from two states Delta (28%) and Lagos (26%). Age-group of 21-40 years was the most affected with a range of 15-51 years and median age of 32 years (NCDC, 2019). As a back drop of the outbreaks, Nigeria commenced the Delphi process in 2017 in which MPX was gradually transitioned into IDSR. Consequently, in 2019 MPX was listed as priority disease for routine reporting (NCDC, 2018;NCDC, 2019). As at the third quarter of 2019 Akwa Ibom State has reported 10 suspected cases, three of these cases had sample collected, two samples were inconclusive and one positive for Monkeypox. These cases were reported in Ikot Enin ward of Mkpat Enin local government area (LGA). However, there was a worry by the number of suspected cases reported with one confirmed; the Monkeypox technical working group identified poor sample collection and management as a bane of inconclusive results from Akwa Ibom State. Consequently, an enhanced case management and surveillance was recommended to investigate and support the earlier result in Akwa Ibom State between 14 th and 24 th October, 2019.

Study Area and Population
Akwa Ibom is a state in Nigeria located in the southern coastal part of the country lying between latitudes 4°32′N and 5°33′N and longitudes 7°25′E and 8°25′E. The state is located in the South-South geopolitical zone and is bordered on the east by Cross River State, by Rivers State and State on the west and by the Atlantic Ocean and the southernmost tip of Cross River State on the south The state's capital is Uyo, with over 500,000 inhabitants

Case Definition of Monkeypox
Suspected case: Any person presenting with a history of sudden onset of fever followed by a vesiculopustular rash occurring mostly on the face, palms and soles of feet. Confirmed Case: Any suspected case with laboratory confirmation (Positive IgM Antibody, PCR or Virus isolation). Contact: Any person who has no symptoms but who has been in physical contact with a suspected case or with body fluids of a case in the last three weeks (i.e. skin secretions, oral secretions, premastication of food, urine, stools, vomiting, blood, sexual contact) (NCDC, 2019a).

Figure 1: Akwa Ibom State LGAs showing Mkpat Enin LGA
We constituted a team which comprised of DSNO, laboratory, and rapid response team (RRT) from NCDC. Retrospective cases were identified from line list and their contact traced. We identified suspected cases and collected samples which were sent to the National Reference laboratory (NRL) Abuja for diagnosis. A structure pre-tested questionnaire assessing knowledge, attitude and practice and risk perception (KAP) of health workers and community members at Ikot Enin Mkpat Enin LGA was administered. Search for active cases of MPX cases was conducted in selected health facilities; the isolation ward of infectious disease hospital Uyo was accessed to determine its capacity to manage MPX cases in the state. We carried out a case control study on the 3 cases (one lab confirmed, 2 epidemiology linked) in Mkpat Enin LGA. Selection of cases was as followed 2 control each (index case, husband and child) were selected from (neighborhood, community controls).

RESULTS
Eight suspected cases of MPX were identified and samples collected from 14 th -24 th October 2019. These cases were clustered within Mkpat Enin LGA in 3 communities (Ikot Enin, Ndom, and Ikot Akpaden). Cases identified included patients with suspected secondary infection, patient's epidemiological linked to confirmed MPX cases and suspected cases identified during active search. Samples were collected from all 8 suspected during the outbreak response were negative for Monkeypox.

Analytical Investigation
We carried out a case control study on the 3 cases in Mkpat Enin LGA from 14-24 October 2019. There were 6 controls comprising 2 controls each (index case, husband and child) control.

Interventions and Training
The team conducted health worker sensitization at the infectious disease hospital (IDH), assessed their level of preparedness to receive and manage Monkeypox cases.
LGAs DSNO, surveillance focal persons and selected nurses were trained on case identification and reporting, sample collection and management including on site mentoring of DSNOs on the filling of data forms (CIFs, Lab forms, line list). House to house and market sensitization in affected communities were carried out. Team also distributed IEC materials to DSNOs for onward distribution to their respective Local government areas.

DISCUSSION
The baseline knowledge of HCW and community members at Ikot Enin was high 17(85%), 12(62%); however, the health seeking behavior of community members was very poor 2(11%). These may be attributed to the alleged rejection of patients by health facilities and health care workers for fear of contacting disease steaming from suspected cases. Stigmatization of patient within the communities was also identified by rapid response team (RRT) as a major reason for the poor health seeking behavior. Consequently, the RRT implored the community members and health care workers avoid stigmatizing the suspected patients. Health care workers were trained on sample collection and management as well as provided with personal protective equipment to protect them when managing the suspected cases.
Consumption of monkeys and giant rats was a key delicacy in affected communities, about 12(86%) of respondent consume monkeys and giant rats, these animals may serve as reservoirs to Monkeypox even though this assertion is still debatable, (CDC, 2019;WHO, 2018). Suspected MPX cases were clustered in Mkpat Enin LGA ( Ikot Enin, Ndom and Ikot Akpaden), the reason for these clustering is not properly understood further studies are recommended to shed more light on same due to the possibility of human to human transmission (Ladnyj, Ziegler, & Kima, 1972;CDC, 1997;Yinka-Ogunleye et al., 2018). There was a general apathy by nurses at the infectious disease hospital (IDH) Uyo to accept suspected cases of MPX identified by rapid response team; however, he HCW identified poor remuneration and skewed attention focused on medical doctors. These findings coupled with an ageing work force at the IDH made the training of staff a herculean task. These findings were brought to the attention of authorities for necessary action. As part of the measures targeted at curbing the tide of MPX in the state, the honorable commissioner of health held a press conference on Friday 25 th October 2019 to sensitize the people of the State about the disease.

CHALLENGES AND LIMITATIONS
The IDH was not in a good State for use throughout the course of the response. The dedicated ambulance for infectious disease patients was not fixed and make functional throughout the course of the stay of the RRT. All the suspected cases were left within the communities until when the results confirmed negative status. As of 24 th October 2019, when the NRRT was leaving the town, none of the suspected cases identified was conveyed to the IDH. The following observations were made paucity of funds to fix the State ambulance to convey the patient; the IDH is not in good condition to receive patients; poor working conditions may have contributed to the perceived unwillingness of the HCWs to receive and manage patients; the number of positive MPX cases was small consequently may affect conclusion deduced from analysis.
It was revealed that without the commitment from the State leadership, the fight against MPX will drag on for years. Integration of the One-health approach should be streamlined at all levels including designing of IEC materials. Community engagement should be strategically integrated into the MPX response (Bottom-Up approaches). Active case search and contact tracing are key to break the transmission of MPX in the community. An early response should be adopted by having in place dedicated funds for emergency. Continuous engagement of the community heads will help to improve case reporting