Infection prevention and control of highly infectious pathogens in resource-limited countries: an experience from Marburg viral disease outbreak in Kagera Region - Tanzania.

Marburg viral disease (MVD) is a highly infectious disease with a case fatality rate of up to 90%, particularly impacting resource-limited countries where implementing Infection Prevention and Control (IPC) measures is challenging. This paper shares the experience of how Tanzania has improved its capacity to prevent and control highly infectious diseases, and how this capacity was utilized during the outbreak of the MVD disease that occurred for the first time in the country in 2023.In 2016 and the subsequent years, Tanzania conducted self and external assessments that revealed limited IPC capacity in responding to highly infectious diseases. To address these gaps, initiatives were undertaken, including the enhancement of IPC readiness through the development and dissemination of guidelines, assessments of healthcare facilities, supportive supervision and mentorship, procurement of supplies, and the renovation or construction of environments to bolster IPC implementation.The official confirmation and declaration of MVD on March 21, 2023, came after five patients had already died of the disease. MVD primarily spreads through contact and presents with severe symptoms, which make patient care and prevention challenging, especially in resource-limited settings. However, with the use of a trained workforce; IPC rapid needs assessment was conducted, identifying specific gaps. Based on the results; mentorship programs were carried out, specific policies and guidelines were developed, security measures were enhanced, all burial activities in the area were supervised, and both patients and staff were monitored across all facilities. By the end of the outbreak response on June 1, 2023, a total of 212 contacts had been identified, with the addition of only three deaths. Invasive procedures like dialysis and Manual Vacuum Aspiration prevented some deaths in infected patients, procedures previously discouraged.In summary, this experience underscores the critical importance of strict adherence to IPC practices in controlling highly infectious diseases. Recommendations for low-income countries include motivating healthcare providers and improving working conditions to enhance commitment in challenging environments. This report offers valuable insights and practical interventions for preparing for and addressing highly infectious disease outbreaks through implementation of IPC measures.

Assessment of the pathogen genomics landscape highlights disparities and challenges for effective AMR Surveillance and outbreak response in the East African community.

The East African Community (EAC) grapples with many challenges in tackling infectious disease threats and antimicrobial resistance (AMR), underscoring the importance of regional and robust pathogen genomics capacities. However, a significant disparity exists among EAC Partner States in harnessing bacterial pathogen sequencing and data analysis capabilities for effective AMR surveillance and outbreak response. This study assesses the current landscape and challenges associated with pathogen next-generation sequencing (NGS) within EAC, explicitly focusing on World Health Organization (WHO) AMR-priority pathogens. The assessment adopts a comprehensive approach, integrating a questionnaire-based survey amongst National Public Health Laboratories (NPHLs) with an analysis of publicly available metadata on bacterial pathogens isolated in the EAC countries. In addition to the heavy reliance on third-party organizations for bacterial NGS, the findings reveal a significant disparity among EAC member States in leveraging bacterial pathogen sequencing and data analysis. Approximately 97% (n = 4,462) of publicly available high-quality bacterial genome assemblies of samples collected in the EAC were processed and analyzed by external organizations, mainly in Europe and North America. Tanzania led in-country sequencing efforts, followed by Kenya and Uganda. The other EAC countries had no publicly available samples or had all their samples sequenced and analyzed outside the region. Insufficient local NGS sequencing facilities, limited bioinformatics expertise, lack of adequate computing resources, and inadequate data-sharing mechanisms are among the most pressing challenges that hinder the EAC's NPHLs from effectively leveraging pathogen genomics data. These insights emphasized the need to strengthen microbial pathogen sequencing and data analysis capabilities within the EAC to empower these laboratories to conduct pathogen sequencing and data analysis independently. Substantial investments in equipment, technology, and capacity-building initiatives are crucial for supporting regional preparedness against infectious disease outbreaks and mitigating the impact of AMR burden. In addition, collaborative efforts should be developed to narrow the gap, remedy regional imbalances, and harmonize NGS data standards. Supporting regional collaboration, strengthening in-country genomics capabilities, and investing in long-term training programs will ultimately improve pathogen data generation and foster a robust NGS-driven AMR surveillance and outbreak response in the EAC, thereby supporting global health initiatives.

Surveillance for sickle cell disease, United Republic of Tanzania.

OBJECTIVE: To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. METHODS: We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. FINDINGS: We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A- deficiency in 19.2% (14/73) of males. CONCLUSION: Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.

Investigation of household contacts of pulmonary tuberculosis patients increases case detection in Mwanza City, Tanzania.

BACKGROUND: Tuberculosis (TB) contact tracing is a key strategy for containing TB and provides addition to the passive case finding approach. However, this practice has not been implemented in Tanzania, where there is unacceptably high treatment gap of 62.1% between cases estimated and cases detected. Therefore calls for more aggressive case finding for TB to close this gap. We aimed to determine the magnitude and predictors of bacteriologically-confirmed pulmonary TB among household contacts of bacteriologically-confirmed pulmonary TB index cases in the city of Mwanza, Tanzania. METHODS: This study was carried out from August to December 2016 in Mwanza city at the TB outpatient clinics of Tertiary Hospital of the Bugando Medical Centre, Sekou-Toure Regional Hospital, and Nyamagana District Hospital. Bacteriologically-confirmed TB index cases diagnosed between May and July 2016 were identified from the laboratory registers book. Contacts were traced by home visits by study TB nurses, and data were collected using a standardized TB screening questionnaire. To detect the bacterioriologically-confirmed pulmonary TB, two sputum samples per household contact were collected under supervision for all household contacts following standard operating procedures. Samples were transported to the Bugando Medical Centre TB laboratory for investigation for TB using fluorescent smear microscopy, GeneXpert MTB/RIF and Löwenstein-Jensen (LJ) culture. Logistic regression was used to determine predictors of bacteriologically-confirmed pulmonary TB among household contacts. RESULTS: During the study period, 456 household contacts from 93 TB index cases were identified. Among these 456 household contacts, 13 (2.9%) were GeneXpert MTB/RIF positive, 18 (3.9%) were MTB-culture positive and four (0.9%) were AFB-smear positive. Overall, 29 (6.4%) of contacts had bacteriologically-confirmed pulmonary TB. Predictors of bacteriologically-confirmed pulmonary TB among household contacts were7being married (Odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-8.0; p = 0.012) and consuming less than three meals a day (OR, 3.7; 95% CI, 1.6-8.7; p = 0.009). CONCLUSIONS: Our data suggest that in Mwanza, Tanzania, seven in 100 contacts living in the same house with a TB patient develop bacteriologically-confirmed pulmonary TB. These results therefore underscore the need to implement routine TB contact tracing to control tuberculosis in high TB burden countries such as Tanzania.

Trends of measles in Tanzania: A 5-year review of case-based surveillance data, 2018-2022.

OBJECTIVES: Tanzania observed a gradual increase in the number of measles cases since 2019 with a large outbreak recorded during 2022. This study describes the trend of measles in Tanzania over a 5-year period from 2018-2022. METHODS: This was a descriptive study conducted using routine measles case-based surveillance system including 195 councils of the United Republic of Tanzania. RESULTS: Between 2018 and 2022 there were 12,253 measles cases reported. Out of 10,691 (87.25%) samples tested by enzyme-linked immunosorbent assay, 903 (8.4%) were measles immunoglobulin M positive. The highest number of laboratory-confirmed measles cases was in 2022 (64.8%), followed by 2020 (13.8%), and 2019 (13.5%). Out of 1279 unvaccinated cases, 213 (16.7%) were laboratory-confirmed measles cases compared to 77/723 (10.6%) who were partially vaccinated and 71/1121 (6.3%) who were fully vaccinated (P < 0.001). Children aged between 1-4 years constituted the most confirmed measles cases after laboratory testing, followed by those aged 5-9 years. There was a notable increase in the number of laboratory-confirmed measles cases in children <1 year and 10-14 years during 2022 compared to previous years. The vaccination coverage of the first dose of measles-containing vaccine (MCV1) was maintained >90% since 2013 while MCV2 increased gradually reaching 88% in 2022. CONCLUSIONS: Accumulation of susceptible children to measles due to suboptimal measles vaccination coverage over the years has resulted in an increase in the number of laboratory-confirmed measles cases in Tanzania with more cases recorded during the COVID-19 pandemic. Strengthening surveillance, routine immunization, and targeted strategies are key to achieving the immunity levels required to interrupt measles outbreaks.

Humoral Immune Responses following COVID-19 Vaccinations among Adults in Tanzania.

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9-97.5) and 98.3% (95%CI: 97.3-99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, (p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups.

Implementation of the laboratory quality management system (ISO 15189): Experience from Bugando Medical Centre Clinical Laboratory - Mwanza, Tanzania.

BACKGROUND: Use of laboratory evidence-based patient health care in Tanzania remains a complex problem, as with many other countries in sub-Saharan Africa. As at 2010, 39 African countries, including Tanzania, had no clinical laboratories that met the minimum requirements for international laboratory standards (International Organization for Standardization [ISO] 15189). OBJECTIVE: The aim of this article is to share experience from Bugando Medical Centre laboratory's milestones in reaching ISO 15189 accreditation. METHODS: Mentors to address the laboratory management and technical requirements performed a gap analysis using the Southern African Development Community Accreditation system checklist. Several non-conformances were detected. System and technical procedures were developed, approved and communicated. Quality indicators were established to measure laboratory improvement and to identify issues which require immediate and preventive actions. RESULTS: The departments' external quality assessment performance increased after ISO 15189 implementation (e.g. Parasitology from 45% to 100%, Molecular Biology from no records to 100%, Biochemistry 50% to 95%, Tuberculosis Microscopy 60% to 100%, and Microbiology from 48.1% to 100%). There was a reduction in complaints, from eight to two per week. Rejected samples were reduced from 7.2% to 1.2%. Turn-around time was not recorded before implementation but reached 92% (1644/1786) of the defined targets, and the proportion of contamination in blood cultures decreased from 16% to 4%. CONCLUSION: Our experience suggests that the implementation of a quality management system is possible in resource-limited countries like Tanzania. Mentorship is necessary and should be done by professional laboratory mentors trained in quality management systems. Financial resources and motivated staff are key to achieving ISO 15189 accreditation.

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8-related lymphomas?

We set out to analyze the presence of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in different neoplasms occurring in East Africa, a region characterized by a high KSHV/HHV-8 seroprevalence rate and endemic Kaposi's sarcoma (KS). Our results suggest that, in endemic regions of Africa, KSHV/HHV-8 is predominantly associated with KS, independently of HIV status. During the course of this study, other important information came to light. We found the presence of KSHV/HHV-8 in 2 cases of lymph nodes partially involved by Burkitt's lymphoma and KS and in 1 case of multicentric Castleman disease. Our immunophenotypic and molecular data seem to suggest 2 different mechanisms of viral infection are at work in lymphoid cells. On one hand, when B cells show a latent phase infection with KSHV/HHV-8, after the germinal center reaction, naive B cells become resting memory B cells, similarly to Epstein-Barr virus-infected B cells. On the other hand, when lytic genes such as vIL6 are expressed in naive B cells, they may be driven to differentiate into plasmablasts without undergoing germinal center reaction. Interestingly, among KSHV/HHV-8-positive cases, in those in which there was also lymphoma, the neoplastic cells were negative for KSHV/HHV-8. This further confirms that KSHV/HHV-8 is involved in the neoplastic transformation of only certain types of lymphoma, probably in relation to their precursor infected cell. In conclusion, the maturation stage of KSHV/HHV-8-positive B cells as well as the type of viral infection may well determine the morphological, phenotypic, and clinical characteristics of KSHV/HHV-8-associated lymphomas.