Analysis of sociodemographic and clinical factors associated with Lassa fever disease and mortality in Nigeria.

Over past decades, there has been increasing geographical spread of Lassa fever (LF) cases across Nigeria and other countries in West Africa. This increase has been associated with significant morbidity and mortality despite increasing focus on the disease by both local and international scientists. Many of these studies on LF have been limited to few specialised centres in the country. This study was done to identify sociodemographic and clinical predictors of LF disease and related deaths across Nigeria. We analysed retrospective surveillance data on suspected LF cases collected during January-June 2018 and 2019. Multivariable logistic regression analyses were used to identify the factors independently associated with laboratory-confirmed LF diagnosis, and with LF-related deaths. There were confirmed 815 of 1991 suspected LF cases with complete records during this period. Of these, 724/815 confirmed cases had known clinical outcomes, of whom 100 died. LF confirmation was associated with presentation of gastrointestinal tract (aOR 3.47, 95% CI: 2.79-4.32), ear, nose and throat (aOR 2.73, 95% CI: 1.80-4.15), general systemic (aOR 2.12, 95% CI: 1.65-2.70) and chest/respiratory (aOR 1.71, 95% CI: 1.28-2.29) symptoms. Other factors were being male (aOR 1.32, 95% CI: 1.06-1.63), doing business/trading (aOR 2.16, 95% CI: 1.47-3.16) and farming (aOR 1.73, 95% CI: 1.12-2.68). Factors associated with LF mortality were a one-year increase in age (aOR 1.03, 95% CI: 1.01-1.04), bleeding (aOR 2.07, 95% CI: 1.07-4.00), and central nervous manifestations (aOR 5.02, 95% CI: 3.12-10.16). Diverse factors were associated with both LF disease and related death. A closer look at patterns of clinical variables would be helpful to support early detection and management of cases. The findings would also be useful for planning preparedness and response interventions against LF in the country and region.

Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021.

BACKGROUND: With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria. METHODS: We conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13. RESULTS: There were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66 121 (18.2%) and 91 644 (20.8%) tested positive in the first and second waves, respectively. There was a 21.3% increase in the number of tests conducted in the second wave with TPR increasing by 14.3%. CI during the first and second waves were 30.3/100 000 and 42.0/100 000 respectively. During the second wave, confirmed COVID-19 cases increased among females and people 30 years old or younger and decreased among urban residents and individuals with travel history within 14 days of sample collection (p value <0.001). Most confirmed cases were asymptomatic at diagnosis during both waves: 74.9% in the first wave; 79.7% in the second wave. CFR decreased during the second wave (0.7%) compared with the first wave (1.8%). CONCLUSION: Nigeria experienced a larger but less severe second wave of COVID-19. Continued implementation of public health and social measures is needed to mitigate the resurgence of another wave.

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study.

BACKGROUND: Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. METHODS: We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. RESULTS: Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. CONCLUSIONS: Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

Descriptive epidemiology of cholera outbreak in Nigeria, January-November, 2018: implications for the global roadmap strategy.

BACKGROUND: The cholera outbreak in 2018 in Nigeria reaffirms its public health threat to the country. Evidence on the current epidemiology of cholera required for the design and implementation of appropriate interventions towards attaining the global roadmap strategic goals for cholera elimination however seems lacking. Thus, this study aimed at addressing this gap by describing the epidemiology of the 2018 cholera outbreak in Nigeria. METHODS: This was a retrospective analysis of surveillance data collected between January 1st and November 19th, 2018. A cholera case was defined as an individual aged 2 years or older presenting with acute watery diarrhoea and severe dehydration or dying from acute watery diarrhoea. Descriptive analyses were performed and presented with respect to person, time and place using appropriate statistics. RESULTS: There were 43,996 cholera cases and 836 cholera deaths across 20 states in Nigeria during the outbreak period, with an attack rate (AR) of 127.43/100,000 population and a case fatality rate (CFR) of 1.90%. Individuals aged 15 years or older (47.76%) were the most affected age group, but the proportion of affected males and females was about the same (49.00 and 51.00% respectively). The outbreak was characterised by four distinct epidemic waves, with higher number of deaths recorded in the third and fourth waves. States from the north-west and north-east regions of the country recorded the highest ARs while those from the north-central recorded the highest CFRs. CONCLUSION: The severity and wide-geographical distribution of cholera cases and deaths during the 2018 outbreak are indicative of an elevated burden, which was more notable in the northern region of the country. Overall, the findings reaffirm the strategic role of a multi-sectoral approach in the design and implementation of public health interventions aimed at preventing and controlling cholera in Nigeria.

Measures to control protracted large Lassa fever outbreak in Nigeria, 1 January to 28 April 2019.

Lassa fever cases have increased in Nigeria since 2016 with the highest number, 633 cases, reported in 2018. From 1 January to 28 April 2019, 554 laboratory-confirmed cases including 124 deaths were reported in 21 states in Nigeria. A public health emergency was declared on 22 January by the Nigeria Centre for Disease Control. We describe the various outbreak responses that have been implemented, including establishment of emergency thresholds and guidelines for case management.

Impact of a behaviour change communication programme on net durability in eastern Uganda.

BACKGROUND: The importance of net durability and the average useful life of a net is increasingly recognized as one of the critical factors that determine how often nets need to be replaced. A study to assess the effect of a net care and repair behaviour change communication (BCC) programme on net durability was conducted in one district in Eastern Uganda with a district in a neighbouring region serving as a comparison. Both districts had received LLINs in September of 2012. METHODS: The intervention was comprised of radio programmes, school and community events. Two-stage cluster sampling household surveys to assess net condition, exposure to BCC messages, and attitudes towards net care and repair were conducted in both districts at baseline (2-3 months post net distribution) and endline (20-21 months post distribution). Net condition was assessed using the proportionate hole index, with nets being classified as either serviceable or too torn. RESULTS: The intervention led to an additional 31.2 % increased exposure to net care and repair messages in the intervention district. Respondents in the intervention district had a more positive attitude towards net care and repair (32 % of respondents were classified as having a very positive attitude compared to 10 % in the comparison district), which was positively associated with the number of channels through which messages had been received (P < 0.001). Nets belonging to respondents with a very positive attitude were more often categorized as serviceable (80.2 %) compared to respondents with a poor/average attitude (66.4 %; odds ratio: 2.05, P = 0.028); however, this was only observed for the net brand with the greater physical integrity. Additionally, socio-economic status was a significant predictor of net condition. Although nets in the intervention district had significantly more repairs done per net, the act of repairing alone did not improve net condition. CONCLUSIONS: In conclusion, the evaluation showed that the BCC programme resulted in improved knowledge and attitudes towards care and repair, which impacted positively on net condition. Repairs alone were not sufficient to improve net condition. Additional research on which care behaviours and attitudes are most associated with improved net condition would help BCC planners hone their campaigns.

Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4⁺ cell counts: findings from a cluster-randomized trial.

OBJECTIVES: African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease. METHODS: The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4⁺ cell count less than 50 cells/µl and those who presented with higher CD4⁺ cell counts. We used Kaplan-Meier methods and Poisson regression. RESULTS: Four hundred and forty four of 1453 (31%) participants had baseline CD4⁺ cell count less than 50 cells/µl. Overall, 110 (25%) deaths occurred among participants with baseline CD4⁺ cell count less than 50  cells/µl and 87 (9%) in those with higher CD4⁺ cell count. Among participants with CD4 cell count less than 50  cells/µl, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53-1.18] compared with 1.22 (95% CI 0.78-1.89) for those who presented with higher CD4⁺ cell count. CONCLUSION: HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4⁺ cell count. This emphasises the critical role of adherence to antiretroviral therapy.

Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study.

BACKGROUND: There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions. METHODS: Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses. RESULTS: 1453 subjects were enrolled with baseline median count of 108 cells/µl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 - 0.91), 0.86 (0.84 - 0.88) and 0.85 (0.83 - 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death. CONCLUSION: Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.

Comparison of home and clinic-based HIV testing among household members of persons taking antiretroviral therapy in Uganda: results from a randomized trial.

OBJECTIVE: Due to high rates of undiagnosed and untreated HIV infection in Africa, we compared HIV counseling and testing (VCT) uptake among household members of patients receiving antiretroviral therapy. METHODS: HIV-infected persons attending an AIDS clinic were randomized to a home-based or clinic-based antiretroviral therapy program including VCT for household members. Clinic arm participants were given free VCT vouchers and encouraged to invite their household members to the clinic for VCT. Home arm participants were visited, and their household members offered VCT using a 3-test rapid finger-stick testing algorithm. VCT uptake and HIV prevalence were compared. FINDINGS: Of 7184 household members, 3974 (55.3%) were female and 4798 (66.8%) were in the home arm. Home arm household members were more likely to receive VCT than those from the clinic arm (55.8% vs. 10.9%, odds ratio: 10.41, 95% confidence interval: 7.89 to 13.73; P < 0.001), although the proportion of HIV-infected household members was higher in the clinic arm (17.3% vs. 7.1%, odds ratio: 2.76, 95% confidence interval: 1.97 to 3.86, P < 0.001). HIV prevalence among all household members tested in the home arm was 56% compared with 27% in the clinic arm. Of 148 spouses of HIV-infected patients, 69 (46.6%) were uninfected. Persons aged 15-24 were less likely to test than other age groups, and in the home arm, women were more likely to test than men. CONCLUSIONS: Home-based VCT for household members of HIV-infected persons was feasible, associated with lower prevalence, higher uptake, and increased identification of HIV-infected persons than clinic-based provision.

Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial.

BACKGROUND: Identification of new ways to increase access to antiretroviral therapy in Africa is an urgent priority. We assessed whether home-based HIV care was as effective as was facility-based care. METHODS: We undertook a cluster-randomised equivalence trial in Jinja, Uganda. 44 geographical areas in nine strata, defined according to ratio of urban and rural participants and distance from the clinic, were randomised to home-based or facility-based care by drawing sealed cards from a box. The trial was integrated into normal service delivery. All patients with WHO stage IV or late stage III disease or CD4-cell counts fewer than 200 cells per microL who started antiretroviral therapy between Feb 15, 2005, and Dec 19, 2006, were eligible, apart from those living on islands. Follow-up continued until Jan 31, 2009. The primary endpoint was virological failure, defined as RNA more than 500 copies per mL after 6 months of treatment. The margin of equivalence was 9% (equivalence limits 0.69-1.45). Analyses were by intention to treat and adjusted for baseline CD4-cell count and study stratum. This trial is registered at http://isrctn.org, number ISRCTN 17184129. FINDINGS: 859 patients (22 clusters) were randomly assigned to home and 594 (22 clusters) to facility care. During the first year, 93 (11%) receiving home care and 66 (11%) receiving facility care died, 29 (3%) receiving home and 36 (6%) receiving facility care withdrew, and 8 (1%) receiving home and 9 (2%) receiving facility care were lost to follow-up. 117 of 729 (16%) in home care had virological failure versus 80 of 483 (17%) in facility care: rates per 100 person-years were 8.19 (95% CI 6.84-9.82) for home and 8.67 (6.96-10.79) for facility care (rate ratio [RR] 1.04, 0.78-1.40; equivalence shown). Two patients from each group were immediately lost to follow-up. Mortality rates were similar between groups (0.95 [0.71-1.28]). 97 of 857 (11%) patients in home and 75 of 592 (13%) in facility care were admitted at least once (0.91, 0.64-1.28). INTERPRETATION: This home-based HIV-care strategy is as effective as is a clinic-based strategy, and therefore could enable improved and equitable access to HIV treatment, especially in areas with poor infrastructure and access to clinic care.

Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda.

BACKGROUND: In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4-12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates. METHODS: HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4-6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression. RESULTS: 4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport. CONCLUSION: About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.

Integrating research into routine service delivery in an antiretroviral treatment programme: lessons learnt from a cluster randomized trial comparing strategies of HIV care in Jinja, Uganda.

Trials integrated into normal health service delivery are designed to evaluate the effectiveness of interventions under real-life conditions. However, integrating research into service delivery creates many operational challenges and raises ethical dilemmas. Here we discuss the operational and ethical issues arising from such trials using the example of a cluster randomized trial evaluating two strategies of ART delivery in Jinja, south-east Uganda.

Use of WHO clinical stage for assessing patient eligibility to antiretroviral therapy in a routine health service setting in Jinja, Uganda.

In a routine service delivery setting in Uganda, we assessed the ability of the WHO clinical stage to accurately identify HIV-infected patients in whom antiretroviral therapy should be started. Among 4302 subjects screened for ART, the sensitivity and specificity (95% CI) of WHO stage III, IV against a CD4 count < 200 x 106/l were 52% (50, 54%) and 68% (66, 70%) respectively. Plasma viral load was tested in a subset of 1453 subjects in whom ART was initiated. Among 938 subjects with plasma viral load of 100,000 copies or more, 391 (42%, 95% CI 39, 45%) were at WHO stage I or II. In this setting, a large number of individuals could have been denied access to antiretroviral therapy if eligibility to ART was assessed on the basis of WHO clinical stage. There is an urgent need for greater CD4 count testing and evaluation of the utility of plasma viral load prior to initiation of ART to accompany the roll-out of ART.

A cluster-randomised trial to compare home-based with health facility-based antiretroviral treatment in Uganda: study design and baseline findings.

The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We report the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 106 cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load > or =100,000 copies. Baseline characteristics did not change over time. Considerably fewer men than women presented for treatment. Both men and women presented at an advanced stage with very low median CD4 count and high plasma viral load.