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. 2024 Sep 5;19(9):e0309762. doi: 10.1371/journal.pone.0309762

Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern Tanzania

Vida Mmbaga 1, George Mrema 1,2,*, Danstan Ngenzi 1, Welema Magoge 1, Emmanuel Mwakapasa 1, Frank Jacob 1, Hamza Matimba 3, Medard Beyanga 3, Angela Samweli 4, Michael Kiremeji 4, Mary Kitambi 4, Erasto Sylvanus 4, Ernest Kyungu 5, Gerald Manase 5, Joseph Hokororo 6, Christer Kanyankole 7, Martin Rwabilimbo 7, Issessanda Kaniki 7, George Kauki 8, Maria Ezekiely Kelly 8, William Mwengee 8, Gabriel Ayeni 8, Faraja Msemwa 8, Grace Saguti 8, George S Mgomella 9, Kokuhabwa Mukurasi 9, Marcelina Mponela 9, Eliakimu Kapyolo 10, Jonathan Mcharo 10, Mary Mayige 10, Wangeci Gatei 9, Ishata Conteh 11, Peter Mala 12, Mahesh Swaminathan 9, Pius Horumpende 13, Paschal Ruggajo 13, Grace Magembe 14, Zabulon Yoti 8, Elias Kwesi 4, Tumaini Nagu 15
Editor: Masahiro Kajihara16
PMCID: PMC11376503  PMID: 39236024

Abstract

Introduction

In March 2023, a Marburg Virus Disease (MVD) outbreak was declared in Kagera region, Northwestern Tanzania. This was the first MVD outbreak in the country. We describe the epidemiological characteristics of MVD cases and contacts.

Methods

The Ministry of Health activated an outbreak response team. Outbreak investigation methods were applied to cases identified through MVD standard case definitions and confirmed through reverse-transcriptase polymerase chain reaction (RT PCR). All identified case contacts were added into the contact listing form and followed up in-person daily for any signs or symptoms for 21 days. Data collected from various forms was managed and analyzed using Excel and QGIS software for mapping.

Results

A total of nine MVD cases were reported with eight laboratory-confirmed and one probable. Two of the reported cases were frontline healthcare workers and seven were family related members. Cases were children and adults between 1–59 years of age with a median age of 34 years. Six were males. Six cases died equivalent to a case fatality rate (CFR) of 66.7%. A total of 212 individuals were identified as contacts and two (2) became cases. The outbreak was localized in two geo-administrative wards (Maruku and Kanyangereko) of Bukoba District Council.

Conclusion

Transmission during this outbreak occurred among family members and healthcare workers who provided care to the cases. The delay in detection aggravated the spread and possibly the consequent fatality but once confirmed the swift response stemmed further transmission containing the disease at the epicenter wards. The outbreak lasted for 72 days but as the origin is still unknown, further research is required to explore the source of this outbreak.

Introduction

Marburg virus disease (MVD) is a severe and highly fatal viral infection caused by the Marburg virus. MVD is known for its severe hemorrhagic fever symptoms, including high fever, headaches, muscle pain, and bleeding from various parts of the body [1]. Within Filoviridae family, there are two distinct genera, Orthomarburgvirus and Orthoebolavirus responsible for causing highly contagious viral hemorrhagic fevers. The Orthomarburgvirus genus contains a unique species, Orthomarburgvirus marburgense, with two members Marburg virus (MARV) and Ravn virus (RAVV) [2]. Studies have shown that Fruit bats (Rousettus aegyptiacus) are the natural hosts and reservoirs for the MARV [36].

MARV was discovered in 1967 after infected monkeys were brought to laboratories in Marburg (Germany) and Belgrade (former Yugoslavia) from Uganda causing laboratory-based MVD outbreaks in the respective cities [7, 8]. There have been outbreaks in several African countries, including Kenya (1987), the Democratic Republic of Congo (1998), Angola (2005), Uganda (2007, 2012, 2014, 2017), and Equatorial Guinea (2023) [916]. In 2008, the virus was also detected in the United States of America (USA) and the Netherlands after travelers returned from Uganda and had visited a popular fruit bat cave in a national park [1, 17].

On September 20, 2022, an outbreak of Sudan Virus Disease (SVD) caused by Orthoebolavirus sudanense was declared by the government of Uganda in Mubende district Western Uganda. The outbreak, which recorded 164 cases (142 confirmed and 22 probable) and 77 deaths (55 confirmed and 22 probable), was declared over in January 2023 [18]. This outbreak spread to nine districts, including Masaka City in southern Uganda, which is approximately 90 km (55 miles) from Mutukula town in Kagera region, Tanzania. SVD and MVD share common symptoms and are both transmitted through contact [19]. The outbreak of SVD in Uganda led the Tanzania Ministry of Health (MOH) and its partners to activate preparedness and operational readiness in the Kagera region, which was vital in responding to MVD. Extensive training in events-based surveillance (EBS) was carried out at the community level, and a mobile laboratory equipped with viral hemorrhagic fever (VHF) testing capabilities was strategically placed in the region. Additionally, a simulation exercise for responding to SVD was also carried out in Kagera region in February 2023.

On March 21, 2023, the first MVD outbreak was declared in Kagera region, in the northwestern part of Tanzania, following laboratory confirmation from samples collected from a cluster of illnesses and deaths in two wards in Bukoba district between March 14 and 16, 2023. The outbreak lasted for 72 days and was declared over by the Tanzania MOH on June 1, 2023. This article describes the epidemiological characteristics of cases and contacts of MVD outbreaks to inform future outbreak prevention, preparedness, and response measures.

Methods

Outbreak area

The outbreak occurred in Kagera region located in Northwestern Tanzania. Kagera region borders Rwanda to the west and Burundi to the southwest. To the north, Kagera region shares a border with Uganda, where previous MVD outbreaks have been reported [11, 12, 14, 15].

It has an area of 1,654 square kilometers, 28 wards, and a population of 2, 989, 299 people according to the 2022 Tanzania Population and Housing Census [20]. The residents engage in various economic activities such as cultivation, animal husbandry, fishing, and commerce.

Formulation of outbreak response team

Following the official declaration of the outbreak, the Tanzania Ministry of Health (MOH) created a dual-level response team at the national and regional levels. The response teams were composed of multidisciplinary experts led by incident managers. The national level team was responsible for providing leadership, technical support, formulating guidelines and standard operating procedures, as well as mobilizing resources while the regional response teams led in all response operations. Teams were organized into eight pillars: coordination, case management, surveillance, laboratory and sample management, logistics, psychosocial support, risk communication community engagement (RCCE), water sanitation and hygiene (WASH), and point of entry (PoE). Specialists from national and international partners joined the respective response pillars at the regional level. Residents from the Field Epidemiology and Laboratory Training Program (FELTP) were also deployed throughout the outbreak period supporting different pillars.

Case findings

Case finding was conducted by dedicated Rapid Response Teams (RRTs), consisting of surveillance officers, laboratory experts, and clinicians. The RRTs were deployed to investigate verified MVD alerts from health facilities or the community rapidly completing preliminary investigations. The working MVD case definition was adopted from the World Health Organization (WHO)’s VHF case definitions and included suspect probable and confirmed cases [21].

A suspected case was defined as any person who lived in or had traveled to Kagera Region in the last 21 days (three weeks) and had the following features (i) three or more symptoms consistent with MVD: Fever of 38.0°C (or 37.5°C axillary) or higher, headache, vomiting, nausea, diarrhea, abdominal pain, loss of appetite, general body weakness, aching muscles or joints, unexplained bleeding, cough, rash, difficulty swallowing, difficulty in breathing, hiccups and convulsions, (ii) presenting with unexplained bleeding (in vomitus, stool or diarrhea; bleeding from nose, eyes, mouth and/or skin) and (iii) any sudden and unexplained death. A probable case was any person (dead or alive) meeting the suspect case definition, who had an epidemiological link with a confirmed MVD case (dead or alive) but was not tested or did not have a laboratory confirmation. A confirmed case was any suspected or probable case dead or alive with a positive laboratory result for Marburg virus by reverse-transcriptase polymerase chain reaction (RT-PCR). These MVD Standardized Case Definitions (SCD) were distributed in all health facilities and PoE.

After the RRT’s verification and confirmation that a case met the SCD, a Case Investigation Form (CIF) was completed which was subsequently transformed to populate the line list which contains key information about each case, and a sample was collected and sent to an established mobile laboratory in the outbreak area for RT-PCR testing. The assay used to confirm the outbreak was Altona Diagnostics RealStar® Filovirus Screen RT-PCR capable of detecting various Orthoebolaviruses and distinguishing Marburg virus. The samples were tested at the mobile laboratory and transported to the National Public Health Laboratory (NPHL) in Dar es Salaam for confirmation.

To enhance case finding, an alert desk and additional hotline numbers were established at the regional level, complementing the pre-existing full-time, toll-free number (199) that the MOH utilizes for receiving alerts from the public. To facilitate community reporting of alerts, community alert cards containing symptoms of MVD were introduced and distributed to the community.

Contact tracing and follow-up

Contact tracing was done by a team comprising surveillance officers, data experts, field supervisors and tracer teams. The contact was defined as a person who interacted with a symptomatic MVD case (probable or confirmed) in at least one of the following manners: touched body fluids of the MVD case (blood, vomit, saliva, urine, feces, semen, tears, sweat), had direct physical contact with the body of the patient (alive or dead), touched or cleaned the linens, clothes, or dishes of the patient, or slept or ate in the same household with the patient. During the outbreak, people who met this definition were identified, isolated, and followed up. Identified contacts were documented using contact listing forms. Contacts who were healthcare workers were quarantined at designated hotels while other contacts were quarantined at home. Tracer team members visited contacts daily for 21 days assessing their status by asking about symptoms of MVD and contact information obtained was recorded in contact follow-up forms. Any contact who developed symptoms was re-classified as a suspect case and transferred to the Marburg Treatment Unit (MTU) for isolation and management. Contacts completing their 21-day follow-up were released from quarantine.

Data collection

In this study data was extracted from November 13 to December 3, 2023 from information on MVD cases and contacts that were collected during the outbreak. Information was obtained from archived Case Investigation Forms, Contact Listing Forms, and Contact Follow-up forms. In addition, family members were contacted during data collection to gather information about the whereabouts of cases and any possible connections to other cases.

Data management and analysis

Microsoft Excel (version 2019) was used to enter, clean, and analyze data. Epidemiological descriptive analysis based on time, place, and persons were performed. In addition, the QGIS software 3.26.3 was used to map the distribution of cases and contacts in the study area using openly available shape files accessed through Tanzania’s National Bureau of Statistics. Results and findings are presented using narration, figures, tables, and maps.

Ethical consideration

The information reported in this article represents data collected during the MVD outbreak response. An outbreak investigation is regarded as an emergency activity and was endorsed by MOH officials and didn’t get ethical approval however permission to analyze and publish this information was sought and granted from the Medical Research Coordinating Committee of the National Institute for Medical Research. Relatives of MVD cases provided oral consent before the interview. All personal information collected was treated with high confidentiality, and the presented data is anonymized.

Results

Timeline of onset of symptoms among cases

The probable index case started showing symptoms on February 27, 2023, and died on March 1, 2023. Six cases started showing symptoms between 9 to 14 days after the probable index started showing symptoms and four died. The final case displayed symptoms on April 11, 2023, no additional cases were reported for a continuous period of 42 days. Consequently, on June 1, 2023, the outbreak was officially declared to be over. The MVD epi curve with chronological date of onset and disease outcome is shown in Fig 1.

Fig 1. Epi curve for MVD cases and deaths in Bukoba District, Kagera region, Tanzania from February 27 to May 31, 2023.

Fig 1

Description and epidemiological linkage of MVD cases

A total of nine cases were reported of which eight were confirmed and one was probable. The age of cases ranged from 1–59 years with a median age of 34 years. Of all the cases, six were males, seven were family-related, and two were frontline healthcare workers. Six cases died, making the case fatality of 66.7%. The cases were identified based on the date seen at the health facility; onset of symptoms was based on the case investigation done during the response. Description for individual case reports is given below:

Case 1: A 33-year-old fisherman from Butayaibega village who conducts his fishing activities around the islands in Lake Victoria, where there is a significant population movement for fishing trade, including individuals from neighboring country Uganda. Moreover, the islands and Bukoba town where he lives have large caves that harbors bats, whose manure is used for small-scale farming.

On February 26, 2023, he returned from his fishing activities and attended a wedding in the same village. The next day, he started experiencing headache and fever. At first, his family believed these symptoms were related to previous health problems he had experienced, such as vomiting blood and abdominal pain, which had occurred about two weeks before this event. Instead of seeking immediate medical care, the family opted for home care and moved the fisherman between relatives. He was cared for by his elderly uncle on February 27, 2023, and then transferred to his aunt’s house on February 28, 2023, where his mother (Case 4), cousin (Case 6), and sister (Case 9) provided care. Two other sisters who were in close contact with him showed no symptoms during the 21-day follow-up period. By the night of February 28, 2023, the fisherman’s condition had worsened significantly, with symptoms of vomiting blood and extreme weakness. He was then taken to the local Health Centre in Maruku with the help of villagers, where healthcare workers (Case 5 and Case 7) attended to him. A routine malaria rapid test was conducted by the laboratory personnel (Case 5). On March 1, 2023, he was referred to the Regional Referral Hospital (RRH) in Bukoba, accompanied by relatives, including case 3, in a private vehicle. He passed away on the way to RRH. No MVD laboratory sample was collected during his illness.

Following his death, his body was transported back to his uncle’s house in the same vehicle used for his hospital transfer. Two relatives (added to the contacts) performed traditional cleaning rituals without any guidance or oversight from health care professionals trained in infection prevention and control (IPC); he was buried on March 2, 2023.

Case 2: This was a laboratory confirmed, 50-year-old female, who was the aunt of the probable index case (Case 1), lived in the same neighborhood, and cared for the probable index case at her home. She shared her household with 19 family members, including her son (Case 6). During the index case’s illness, case 2 and her four daughters, residing in the same household, provided care.

Case 2 was initially in good health. Starting on March 10, she developed symptoms including headaches, fatigue, and vomiting. She sought medical assistance and was temporarily admitted to the local Health Centre for observation on March 12, 2023. She was later discharged with medication to be taken at home. On March 13, 2023, her sister-in-law (Case 4) visited her to check on her well-being, and she mentioned that she was also feeling unwell. Despite being discharged with treatment instructions, her condition worsened on March 14, 2023 and she was readmitted to the local Health Centre before being transferred to RRH in Bukoba.

Case 2 symptoms at RRH included fever, general body weakness, and vomiting blood, with a diagnosis of upper gastrointestinal bleeding. She passed away on March 15, 2023. Nasopharyngeal swab for laboratory testing was collected on March 16, 2023 while deceased and the results were available on the same day. Her body was temporarily kept at the RRH mortuary and received a supervised dignified burial on March 16, 2023.

Case 3: The second laboratory confirmed case was a 27-year-old man who was the cousin of the probable index case. He lived in Maruku and operated a local small business. He escorted the probable index case while being transferred from first local Health Centre to RRH in Bukoba. His illness began on March 9, 2023, with unspecified initial symptoms. He sought medical attention at first local Health Centre on March 12, 2023, and was referred to local Town Health Centre. From there, he was eventually transferred to RRH. By then he was presenting with bleeding from various orifices and episodes of convulsion.

He passed away on March 16, 2023, and his body was temporarily kept at the RRH mortuary. Nasopharyngeal swab for laboratory testing was collected on March 16, 2023, while deceased and the results were available on the same day. He received a dignified and supervised burial on March 17, 2023.

Case 4: The third laboratory confirmed case was a 59-year-old female and the mother of the probable index case. She lived in the same neighborhood as Case 2, where the probable index case received care while ill. She started experiencing symptoms of fever, headache, vomiting, abdominal pain, lethargy, anorexia, and difficulty breathing on March 12, 2023.

On March 13, 2023, she sought medical assistance at a first local dispensary, using a private motorcycle ("Boda-boda") ride as transportation. Her daughter (Case 9) accompanied her during this visit. However, her condition worsened on March 14, 2023, and she returned to the first local dispensary, again using the same Boda-boda. She was then referred to Town Health Centre. Unfortunately, she passed away on March 15, 2023. Nasopharyngeal swab for laboratory testing was collected on March 16, 2023 while deceased and the results were available on the same day. She received a supervised and dignified burial on March 16, 2023.

Case 5: The fourth laboratory confirmed case was a 47-year-old male health worker who conducted routine laboratory testing (i.e., malaria rapid test) for the probable index case on March 1, 2023. On March 10, 2023, he began to experience symptoms of illness, including fatigue, fever, headache, and vomiting blood. March 13, 2023, he sought medical attention and was admitted to the Town Health Centre. As his condition worsened, he was transferred to the RRH on March 15, 2023, where he received care from multiple healthcare workers equipped with standard personal protective equipment (PPE). Unfortunately, he passed away on March 16, 2023. Nasopharyngeal swab for laboratory testing was collected on March 16, 2023 while deceased and the results were available on the same day., He received a supervised and dignified burial.

Case 6: The fifth laboratory confirmed case was a 26-year-old male, who is the son of Case 2 and a cousin to the probable index case. He lived in the same household as his mother (Case 2), where the probable index case received care while ill. On March 8, 2023, he developed symptoms, including fever, headache, and general body weakness. In response to his symptoms, he was initially admitted to second local Dispensary (in Ntoma) on March 9, 2023, for one day but was discharged on March 10, 2023, with instructions to continue treatment as an outpatient. However, on March 15, 2023, his condition worsened and was readmitted to the first local Health Centre. On March 16, 2023, he was confirmed to be MVD case and was transferred to the Marburg Treatment Unit in Kabyaile and continued with treatment. He responded well to treatment and survived; he was discharged on April 4, 2023.

Case 7: The sixth laboratory confirmed case was a 35-year-old male, who was a health care worker, and provided care to probable index case, case 4 and case 5 from February 28,2023 onwards. He began showing symptoms on March 8, 2023, including fever, headache, diarrhea, and vomiting blood. Despite feeling unwell, he continued to provide care to other patients.

At first, after feeling ill, he visited the nearby health facility, where he was diagnosed and treated for malaria with Artemether Lumefantrine (ALU). Without improvement, his treatment was changed to high-dose Gentamycin injections.

On March 15, he was referred to the RRH where acute renal failure was diagnosed. On March 16, a sample was taken, and he was confirmed to have MVD. He was isolated and received treatment at the RRH, eventually made a full recovery, on May 22,2023 he was discharged to go home.

Case 8: This seventh laboratory confirmed case was an 18-month-old male child, who was the grandson of Case 4 and the son of Case 9. He was being monitored as a contact of Case 4, who was deceased. On March 19, 2023, the child began to exhibit fever and loss of appetite.

Following the development of symptoms, he tested positive for MVD on March 21, 2023 and was admitted to the MTU on the same day. Despite the medical care, he passed away on April 10, 2023, and received a supervised and dignified burial.

Case 9: The last and eighth laboratory confirmed case was a 38-year-old female, who is the mother of Case 8. She was one of the 212 contacts as she took care of both the probable index case (her brother) and Case 4 (her mother). Due to her child’s young age (Case 8), she had to be admitted with her child to continue caring for him, which is likely how she was exposed to the virus.

On April 10, 2023, she presented with low grade fever, headache, body fatigue, nausea, loss of appetite, vomiting, and heavy vaginal bleeding mixed with clotted blood. She tested positive for MVD on the same day. Additionally, received psychological and social support. Eventually, she recovered and on April 19, 2023, she was discharged as a survivor of MVD.

Description of cases by place

The outbreak was confined to Kagera region in Bukoba District specifically in Maruku and Kanyangereko wards. Moreover, among seven villages in two wards, 5 (55.6%) cases were from Butayaibega village located in Kanyangereko ward (Fig 2).

Fig 2. A map showing distribution of MVD cases in Kagera region, Tanzania from February 27 to May 31, 2023.

Fig 2

Map was drawn using QGIS desktop software 3.26.3. The shapefiles used were from an openly available source (https://www.nbs.go.tz/statistics/topic/gis). The shapefiles were made based on the 2012 population and housing census, but in this study, shapefiles have been modified to capture all the regions information.

Epidemiological description of contacts

A total of 212 individuals were identified as MVD contacts. Females (n = 115 (54.2%)) contributed to the majority of contacts. Contacts between 15–29 and 30–44 years of age accounted for 35.8% and 35.4% of contacts, respectively. Regarding the risk of exposure, 116 (37.9%) and 67 (21.9%) contacts had direct physical contact and body fluid exposure from cases respectively. Most of the contacts were HCWs (n = 89 (42.05%)) followed by family members (n = 87 (41.0%)). Over the course of the follow-up period, 2 (0.9%) developed symptoms and tested positive for MVD. The majority of contacts (n = 117 (55.2%)) were from Bukoba District Council, and most of them resided in Kanyangereko ward (n = 64 (30.3%)) (Table 1 & Fig 3).

Table 1. Characteristics of contacts in Bukoba District, Kagera region from March to May 2023 (n = 212).

Variable Frequency (Percentage)
Sex
Female 115 (54.2)
Male 97 (45.8)
Age group (years)
≤5 14 (6.6)
6–14 12 (5.7)
15–29 76 (35.8)
30–44 75 (35.4)
45–59 27 (12.7)
≥60 8 (3.8)
Type of exposure* (n = 306) **
1 67 (21.9)
2 116 (37.9)
3 39 (12.7)
4 84 (27.5)
Relation of contact to case
Family members 87 (41.0)
Friends 10 (4.7)
HCWs 89 (42.0)
Patients in the same wards 23 (10.8)
Relatives in the ward 2 (0.9)
Security guard 1 (0.5)
Outcome
Graduated 209 (98.6)
Died due to other cause 1 (0.5)
Contact who become case 2 (0.9)
Districts
Bukoba District Council 117 (55.2)
Bukoba Municipal Council 95 (44.8)

* Types of Exposure

1 = Touched body fluids of the MVD case (blood, vomit, saliva, urine, feces, semen, sweat)

2 = Had direct physical contact with the body of the patient (alive or dead)

3 = Touched or cleaned the linens, clothes, or dishes of the patient

4 = Slept or ate in the same household as the patient

** Other contacts had more than one exposure type

Fig 3. Distribution of MVD contacts in Bukoba Districts, Kagera region, Tanzania from February 27 to May 31, 2023.

Fig 3

Map was drawn using QGIS desktop software 3.26.3. The shapefiles used were from an openly available source (https://www.nbs.go.tz/statistics/topic/gis). The shapefiles were made based on the 2012 population and housing census, but in this study, shapefiles have been modified to capture all the regions information.

Discussion

This study describes the first MVD outbreak in Tanzania involving a cluster of cases among closely related family members and frontline healthcare workers. Cases did not spread beyond the initial cluster, a scenario similar to one observed in Eastern Uganda that affected four close family members [12]. Seventeen days passed between the possible onset of illness in the probable index case until laboratory confirmation of subsequent cases. Immediate families were most vulnerable with at least four succumbing to the disease within a span of three days, a scenario that greatly limited potential investigation of exact movements and exposure risks of the initial probable case. Possible initial zoonotic transmission therefore remains unknown, although fruit bats in caves around Bukoba and in other Islands in Lake Victoria where the probable index case may have been fishing, are a common sight. Reports from western Uganda, an area close to Bukoba with reported MVD outbreak in 2015, also document the presence of Rousettus bats that harbor Marburg virus [22].

This outbreak reported a case fatality rate of 67% which is relatively higher when compared to the rates reported in Germany in 1967 (22.6%), Kenya in 1980 (33%), and Uganda in 2012 (58%) [7, 14, 23]. However, higher case fatality rates have been reported in Uganda in 2017 (75%), Angola in 2005 (88%), and DRC Congo in 1998 (83%) [11, 13, 16]. Several factors might have contributed to the observed high case fatality rate. The outbreak was confirmed 17 days after the probable index case showed symptoms despite the probable index and subsequent cases seeking treatment at several healthcare facilities on March 1 and March 8, 2023. Our detailed findings show the low index of suspicion among healthcare workers in all the health facilities that managed the initial cases. One possible explanation for this delay could be due to initial symptoms of MVD often mimicking those of other common endemic diseases prevalent in our local area, such as malaria and typhoid fever [24]. As a result, misdiagnosis can occur and lead to a delay in recognizing MVD as the root cause of the illness.

During this outbreak, only two individuals who had close contact with family members who died from the disease developed symptoms and became cases. This could be attributed to the low transmission rate of the disease in its early stages or was undetected during the outbreak as the Marburg virus can persist in the semen and vaginal excretions of survivors [25]. On the other hand, prompt response within three days following confirming of the outbreak could have played a role in halting the transmission through close monitoring of all identified contacts.

Since the Rift Valley Fever outbreak in 2008, this is the first confirmed VHF outbreak in recent years in Tanzania. The country was able to utilize health security capacities, such as event-based surveillance (EBS), to identify the unknown disease cluster and quickly confirm, respond, and control the MVD by leveraging multisectoral emergency preparedness and response systems. Capacities in place included presence of a mobile laboratory, treatment and isolation facilities, surge training of HCWs on emergency preparedness and response, and trained community health workers on EBS and transportation resources.

Furthermore, the long-standing health systems strengthening from HIV/Tuberculosis, Malaria, and vaccine preventable diseases established service delivery infrastructure. These resources were leveraged to enhance surveillance, scale up infection prevention and control and support case management for better patient outcomes.

Despite the health security capacities, the delay in detection underscores the need for robust and sustained early warning alert and response systems. It is possible the operational VHF readiness efforts in Kagera were waning following the declaration of the end of SVD outbreak in Uganda on January 11, 2023. To strengthen early detection, it is crucial to improve awareness at health facilities about the symptoms of VHF and the associated lab testing to confirm a diagnosis. In addition, the adoption of optimal metrics such as the 7-1-7 approach which aims to measure the detection within 7 days of occurrence, notification of relevant authorities within 1 day and implementation of response measures within 7 days [26] can help identify bottlenecks in response efforts. Moreover, investigations on potential reservoirs and zoonotic transmission dynamics are needed to strengthen health security infrastructure and improve preparedness, readiness, and response in the future.

The inability to identify the origin of the MVD can pose a substantial challenge in terms of preventing future outbreaks.

Conclusion

The transmission of this outbreak was limited to family members and healthcare workers who provided care to the cases. The delay in detection aggravated the spread and possibly the consequent fatality but once confirmed the swift response stemmed further transmission. The outbreak lasted for 72 days and was contained within two neighboring wards in Bukoba District. There is a need to strengthen early detection and reporting at all levels. Further research to investigate the ecological epidemiology of the Marburg virus within Kagera region is highly recommended.

Supporting information

S1 Data

(XLSX)

pone.0309762.s001.xlsx (75.4KB, xlsx)

Acknowledgments

We acknowledge Ministry of Health and President Office Regional Administration Local Government for their swift efforts in containing the Marburg outbreak. Special thanks go to our development partners who actively supported the Tanzanian Ministry of Health during this response. We commend the Kagera Regional/Council Health Management Team and the Mobile Laboratory Staff in Kagera for their leadership and vital contributions in initial investigation of the outbreak, ensuring its containment. We also acknowledge and appreciate the dedication of field supervisors and tracer teams in contact tracing. Lastly, we extend our thanks to the affected villages’ community members and their families for their active role in controlling the outbreak.

Disclaimer: The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the U.S. Centres for Disease Control and Prevention.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Centers for Disease Control and Prevention. About Marburg Virus Disease _ Marburg (Marburg Virus Disease) _ CDC [Internet]. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB); [cited 2023 Jun 23]. Available from: https://www.cdc.gov/vhf/marburg/about.html
  • 2.Biedenkopf N, Bukreyev A, Chandran K, Di Paola N, Formenty PBH, Griffiths A, et al. Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae. Arch Virol [Internet]. 2023;168(8):1–6. Available from: doi: 10.1007/s00705-023-05834-2 [DOI] [PubMed] [Google Scholar]
  • 3.Towner JS, Amman BR, Sealy TK, Reeder Carroll SA, Comer JA, Kemp A, et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009;5(7). doi: 10.1371/journal.ppat.1000536 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Amman BR, Carroll SA, Reed ZD, Sealy TK, Balinandi S, Swanepoel R, et al. Seasonal Pulses of Marburg Virus Circulation in Juvenile Rousettus aegyptiacus Bats Coincide with Periods of Increased Risk of Human Infection. PLoS Pathog. 2012;8(10). doi: 10.1371/journal.ppat.1002877 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Swanepoel R, Smit SB, Rollin PE, Formenty P, Leman PA, Kemp A, et al. Studies of reservoir hosts for Marburg virus. Emerg Infect Dis. 2007;13(12):1847–51. doi: 10.3201/eid1312.071115 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Towner JS, Pourrut X, Albariño CG, Nkogue CN, Bird BH, Grard G, et al. Marburg virus infection detected in a common African bat. PLoS One. 2007;2(8). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Martini GA, Knauff HG, Schmidt HA, Mayer G BG (1968. Marburg virus disease. 1973;(August):542–6. [Google Scholar]
  • 8.Luby JP, Sanders C V. Green monkey disease (“Marburg virus” disease): a new zoonosis. Ann Intern Med. 1969;71(3):657–60. doi: 10.7326/0003-4819-71-3-657 [DOI] [PubMed] [Google Scholar]
  • 9.Johnson ED, Johnson BK, Silverstein D, Tukei P, Geisbert TW, Sanchez AN, et al. Characterization of a new Marburg virus isolated from a 1987 fatal case in Kenya. Arch Virol Suppl. 1996;1996(11):101–14. doi: 10.1007/978-3-7091-7482-1_10 [DOI] [PubMed] [Google Scholar]
  • 10.Faraone J, Liu SL, Ph D. Detection of Marburg Virus Disease in Guinea. 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Id LN, Shoemaker TR, Balinandi S, Chemos G, Kwesiga B, Mulei S, et al. Marburg virus disease outbreak in Kween District Uganda, 2017: Epidemiological and laboratory findings. 2019;1–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Nyakarahuka L, Ojwang J, Tumusiime A, Balinandi S, Whitmer S, Kyazze S, et al. Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014. 2017;23(6). doi: 10.3201/eid2306.170047 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Bausch DG, Borchert M, Grein T, Roth C, Swanepoel R, Libande ML, et al. Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo. Emerg Infect Dis. 2003;9(12):1531–7. doi: 10.3201/eid0912.030355 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Knust B, Schafer IJ, Wamala J, Nyakarahuka L, Okot C, Shoemaker T, et al. Multidistrict Outbreak of Marburg Virus Disease—Uganda, 2012. J Infect Dis. 2015;212(Suppl 2):S119–28. doi: 10.1093/infdis/jiv351 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Adjemian J, Farnon EC, Tschioko F, Wamala JF, Byaruhanga E, Bwire GS, et al. Outbreak of Marburg hemorrhagic fever among miners in kamwenge and ibanda Districts, Uganda, 2007. J Infect Dis. 2011;204(SUPPL. 3):2–5. doi: 10.1093/infdis/jir312 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA, et al. Marburgvirus Genomics and Association with a Large Hemorrhagic Fever Outbreak in Angola. J Virol. 2006;80(13):6497–516. doi: 10.1128/JVI.00069-06 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Timen A. Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands. Emerg Infect Dis. 2009;15(8):1171–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.World Health Organization. Ebola disease caused by Sudan ebolavirus–Uganda [Internet]. World Health Organization. 2023. [cited 2023 Nov 17]. Available from: https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON433 [Google Scholar]
  • 19.Feldmann H, Sanchez A, Geisbert TW. Filoviridae: Marburg and ebola viruses. Fields Virol Sixth Ed. 2013;1. [Google Scholar]
  • 20.National Bureau of Statistics. Administrative Units Population Distribution Report [Internet]. National Population and House Census of Tanzania. National Bureau of Statistics, Dar es Salaam, Tanzania. 2022. Available from: https://www.nbs.go.tz/nbs/takwimu/Census2022/Administrative_units_Population_Distribution_Report_Tanzania_volume1a.pdf [Google Scholar]
  • 21.World Health Organization (WHO). Case definition recommendations for Ebola or Marburg virus diseases. Interim Guidel [Internet]. 2014;(August):1–3. Available from: https://apps.who.int/iris/rest/bitstreams/654926/retrieve [Google Scholar]
  • 22.Amman BR, Jones MEB, Sealy TK, Uebelhoer LS, Schuh AJ, Bird BH, et al. Oral shedding of Marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). J Wildl Dis. 2015;51(1):113–24. doi: 10.7589/2014-08-198 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Johnson BK, Smith DH, Johnson KM, Killey M, Keruga WK. Marburg Virus Disease in Kenya. 1982;816–20. [DOI] [PubMed] [Google Scholar]
  • 24.Kortepeter MG, Bausch DG, Bray M. Basic clinical and Laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011;204(SUPPL. 3). doi: 10.1093/infdis/jir299 [DOI] [PubMed] [Google Scholar]
  • 25.Brainard J, Hooper L, Pond K, Edmunds K, Hunter PR. Risk factors for transmission of Ebola or Marburg virus disease: A systematic review and meta-analysis. Int J Epidemiol. 2016;45(1):102–16. doi: 10.1093/ije/dyv307 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.717 Alliances. 7-1-7 Implementation Toolkit. 2022;(June):2017–9. [Google Scholar]

Decision Letter 0

Masahiro Kajihara

15 Apr 2024

PONE-D-24-07742Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern TanzaniaPLOS ONE

Dear Dr. Mrema,

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Additional Editor Comments:

As highlighted by the reviewers, the manuscript contains a considerable number of editorial and typographical errors, including incomplete sentences and grammatical inaccuracies. Given the significant impact of these issues on the clarity and professionalism of the manuscript, I strongly recommend securing editorial assistance from a proficient English editor well-versed in manuscript formatting best practices. This thorough proofreading process will greatly enhance the quality of the manuscript for the revision process.

Additionally, I kindly request addressing the following minor points, along with considering the reviewers' comments:

1. Please verify the number of samples listed under "Type of exposure" in Table 1. Is it indeed 309, or should it be 306?

2. Ensure that scales are provided for each map in the figures.

3. In Figure 1, please provide an explanation of the numerical values depicted.

Thank you for your attention to these matters.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: No

**********

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Epidemiological description of Marburg virus 1 disease outbreak in Kagera region, Northwestern Tanzania

The authors present an epidemiological description of the MVD outbreak in Tanzania. This is an interesting account of the outbreak response, the cases and circumstances surrounding each case. The manuscript would do with a few minor changes as well editing as explained below.

4. IS THE MANUSCRIPT PRESENTED IN AN INTELLIGIBLE FASHION AND WRITTEN IN STANDARD ENGLISH?

No, it would benefit from some editing of grammatical and typographical errors, as well as rewriting/rephrasing some sentences. Some are noted below.

Page 3:

(i) sentence beginning line 63 to 64 - The etiologies of MVD are RNA viruses………. is incomplete

(ii) sentence beginning line 74 to 77 - The SUDV recorded 164 cases…….. should be rephrased, e.g. There were 164 cases of EVD (142 confirmed and 22 probable) and….

(iii) line 77: Kagera Region - region is capitalised, but through out the manuscript it is all lowercase

Page 5:

(i) line 158: The last sentence is incomplete

(ii) line 161: “information about on…”

Page 7:

(i) line 213: personal (case 5)

Page 8:

(i) sentence beginning line 227: On March 13, 2023, her sister-in-law (Case 4), who was the mother of the index case, visited her, but she also reported feeling unwell.

Page 11:

(i) line 310: here and in other parts of the manuscript fig should be capitalized. Also, if it is in text, it should not be bold.

(ii) Line 322: either should be used with or. In this case either can be removed

(iii) Line 325: “And the majority”

Page 14:

(i) Line 394: there are 2 full stops

(ii) Line 404: the sentence “To strengthen early detection and reporting at all levels.” Seems to be missing something at the beginning.

OTHER COMMENTS

There have been changes to filovirus taxonomy. The authors should follow the International Committee for Taxonomy of Viruses instructions for the taxonomy of Filoviruses. (Biedenkopf, N.; Bukreyev, A.; Chandran, K.; Di Paola, N.; Formenty, P. B. H.; Griffiths, A.; Hume, A. J.; Mühlberger, E.; Netesov, S. V.; Palacios, G.; Pawęska, J. T.; Smither, S.; Takada, A.; Wahl, V.; Kuhn, J. H., Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae. Arch Virol 2023, 168, (8), 220. https://doi.org/10.1007/s00705-023-05834-2.)

Page 3:

Line 73: I suggest it read: “On September 20th, 2022, an outbreak of Ebola virus disease (EVD) caused by Sudan Virus (SUDV) was declared by the government of Uganda in Mubende district Western Uganda.”

This will also allow for the definition of EVD that is in line 83, as in the manuscript it is introduced for the first time, but is not written out in full.

Line 77: I think it is important to indicate that Mutukula town is in Tanzania. This means that line 78 can end “90 km (55 miles) from Mutukula town.” And delete “on the Kagera region (Tanzania), border.”

Line 83: EVD is introduced for the first time, but is not written out in full. If

I think it would be better to add a sentence indicating that EVD and MVD have similar presentation.

Page 7:

Line 188: refers the index. I presume this should read the probable index case. Here and through out the manuscript, it would be better to refer to this case as probable index case and not index case.

Line 204: this is interesting past medical history of vomiting blood. Was there any indication on the timing? Was it the recent past? It may be better to indicate.

Page 10:

Case 7: I think it would be better to indicate form the 1st sentence that Case & treated the index case. This gives a clearer epidemiological picture. Therefore “Index case on 28th February” should move from line 280 to a more appropriate line.

Page 13:

Line 349: it should be clear that the laboratory confirmation was not from the probable index case

Lines 357-360: in this section, the outbreak year has only been given for Uganda. Is there a specific reason? If not, it is better to be consistent and indicate the outbreak year for all or none.

Lines 363-367: it has been documented in literature that ignorance of health care workers about the disease is one of the reasons there is a delay in detection of an outbreak of EVD/MVD, particularly in areas where no previous outbreak has occurred. It would be good to make reference to this.

Lines 368-373: the basic reproduction number for Marburg virus is relatively low. It would be good to make a comment on this aspect.

Line 374-375: best to put (VHF) after viral hemorrhagic fever as it is the first time it is appearing in the manuscript.

Page 14:

Line 388: It would be better to replace SUDV with “the EVD outbreak”

Reviewer #2: line70: the marburg outbreak in Equatorial Guinea occured in 2023...not 2021

line 37-38. What does the sentence "laboratory testing used altona diagnostics realstart filovirus screen RTPCR with at least 2 tests in two separate laboratories" mean? do you mean that the sample sample had to be tested using the same assay in two geographically separate laboratories? if so, why?

line: 156: I think there might be a typo....currently it says that "any contacts who developed symptoms were re-classified as a case....i think you mean "suspect"

line 158: the last sentence is incomplete

line 163: did the reach out to close family members of the individuals involved occur during the outbreak? or afterwards?

Description and epidemiologic linkage of MVD cases: it might be best to summarize the key findings for each patient and place the detailed summaries in the appendix? Also, it would be helpful to provide additional epi details on case 1 (such as his occupation and details on how he might have been infected...some of this information is currently in the discussion section)

line 322-323: what is the difference betweeen family members and relatives?

line 359: would suggest not including the CFR for the Netherlands as it was just 1 patient.

Fig 2: not sure if this figure is necessary

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2024 Sep 5;19(9):e0309762. doi: 10.1371/journal.pone.0309762.r002

Author response to Decision Letter 0


28 May 2024

-We would like to thank the editor and reviewers for their helpful feedback on our manuscript, "Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern Tanzania". Their comments have significantly improved the quality of our work, and we have carefully considered each suggestion in the revised version of the paper. We are confident that we have adequately addressed the raised concerns and that the manuscript is now ready for submission

Attachment

Submitted filename: Response to reviewers comments.docx

pone.0309762.s002.docx (26.6KB, docx)

Decision Letter 1

Masahiro Kajihara

19 Jun 2024

PONE-D-24-07742R1Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern TanzaniaPLOS ONE

Dear Dr. Mrema,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 03 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Masahiro Kajihara, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Regarding my comment 2, "Ensure that scales are provided for each map in the figures," I can accept the current figures even though map scales are not provided (of course, it is better to include them since not all readers are familiar with Tanzania's geology). However, the shapefiles are not available from the URL provided in the legend. Please check the URL again.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: My recommendations on the nomenclature of Filoviruses have not been addressed adequately. The lines 61 to 64 need to be rewritten to convey the correct nomenclature.

The authors should follow the International Committee for Taxonomy of Viruses instructions for the taxonomy of Filoviruses. (Biedenkopf, N.; Bukreyev, A.; Chandran, K.; Di Paola, N.; Formenty, P. B. H.; Griffiths, A.; Hume, A. J.; Mühlberger, E.; Netesov, S. V.; Palacios, G.; Pawęska, J. T.; Smither, S.; Takada, A.; Wahl, V.; Kuhn, J. H., Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae. Arch Virol 2023, 168, (8), 220. https://doi.org/10.1007/s00705-023-05834-2.)

Line 61:

Marburg virus disease has not been renamed as Orthomarburgvirus. Marburg virus disease is caused by the orthomarburgviruses Marburg virus and Ravn virus.

Line 62/63:

The sentence: ‘The virus belongs to the Filoviridae family, which is the same family as the Ebola virus’ is wrong. Ebola virus is one of the orthoebolaviruses and is the representative virus of the species Orthoebolavirus zairense. This sentence needs correct nomenclature as well as English language editing.

Line 63/64:

The sentence ‘Fruit bats (Rousettus aegyptiacus) are widely believed to be the reservoirs of Marburg viruses’

It has been established that R. aegyptiacus are reservoirs of orthomarburgviruses, so it is incorrect to state that they are widely believed to be reservoirs.

Line 77/78:

‘Since EVD and MVD belong to the same family, they share common symptoms and are both transmitted through contact.’

This sentence implies that all viruses belonging to the family Filoviridae share common symptoms. But this is not the case. It would be better to rephrase the sentence to just state that EVD and MVD have common symptoms. Also add a citation for this.

Line 161 -will benefit from English language editing

Line 390: the term SUDV was not replaced by EVD. What is in the manuscript is ‘Ebola’ and not EVD

Reviewer #2: line 36 (abstract): spell out RT-PCR

line 37: instead of "physically followed up" consider followed up in-person

line 43: consider also providing median age as there are extremes in the age range

line 62: consider deleting "and non-human primates" as this list is not exhaustive

line 79: The outbreak in Uganda was due to Sudan virus, so use Sudan virus disease instead of EVD. EVD now only refers to disease due to Ebola virus (species Orthoebolavirus zairense)

line 82: viral hemorrhagic fever should not be capitalized

line 120: for clarity, consider cutting "having any of the following"

line 137: considering using the term orthoebolaviruses instead of EVD as the Altona can detect multiple different orthoebolaviruses

line 137: If you decide to use orthoebolaviruses instead of EVD, considering using the term marburg virus instead of MVD so that you are listing viruses

line 197: consider providing median age (as comment above)

line 225: clarify what you mean by "without any expert supervision" ...i assume this means without IPC supervision?

line 369: malaria and typhoid fever should not be capitalized

line 371: please note that pauci-symptomatic marburg virus disease has been detected in Uganda during follow up serosurveys. Thus it is possible there were more people infected, but were not detected during the outbreak. This is especially important given that Marburg virus can persist in the semen of male survivors

Line 296 – 301: For case 8, what was the date of the positive Marburg test? What was the date of admission to the MTU?

Line 302 – 309: For case 9, it does not seem that she could have been infected by case 1, 4, or 8.

-Assuming an incubation period of 2-21 days and assuming her illness onset date is correct, she was exposed to Marburg virus 24 march – 6 april

-Case 1 died March 1

-Case 4 died March 16

-Case 8 was admitted to the hospital on March 21 and died April 10. Assuming case 8 was admitted to the MTU on March 21 and isolated, the Case 9 (mother of case 8) should not have had any contact with case 8 after he was admitted to the MTU

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2024 Sep 5;19(9):e0309762. doi: 10.1371/journal.pone.0309762.r004

Author response to Decision Letter 1


23 Jul 2024

We would like to express our gratitude to the editor and reviewers for their valuable feedback on our manuscript titled "Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern Tanzania". We have taken into account all of their suggestions and believe that our manuscript has been greatly improved as a result. We are confident that we have addressed all concerns and the revised manuscript is now ready to be re submitted

Attachment

Submitted filename: Response to reviewers comments.docx

pone.0309762.s003.docx (23.4KB, docx)

Decision Letter 2

Masahiro Kajihara

19 Aug 2024

Epidemiological description of Marburg virus disease outbreak in Kagera region, Northwestern Tanzania

PONE-D-24-07742R2

Dear Dr. Mrema,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Masahiro Kajihara, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors present an epidemiological description of the MVD outbreak in Tanzania. This is an interesting account of the outbreak response, the cases and circumstances surrounding each case.

All my comments have been addressed.

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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Acceptance letter

Masahiro Kajihara

26 Aug 2024

PONE-D-24-07742R2

PLOS ONE

Dear Dr. Mrema,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Masahiro Kajihara

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Data

    (XLSX)

    pone.0309762.s001.xlsx (75.4KB, xlsx)
    Attachment

    Submitted filename: Response to reviewers comments.docx

    pone.0309762.s002.docx (26.6KB, docx)
    Attachment

    Submitted filename: Response to reviewers comments.docx

    pone.0309762.s003.docx (23.4KB, docx)

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.


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