Clinical, epidemiological, and spatial features of human rabies cases in Metro Manila, the Philippines from 2006 to 2015.

Rabies remains a public health problem in the Philippines despite the widespread provision of rabies vaccines and rabies immunoglobulin (RIG) as post-exposure prophylaxis (PEP). Detailed descriptions of recent human rabies cases in the Philippines are scarce. This study aimed to describe the clinical, epidemiological, and spatial features of human rabies cases between January 1, 2006, and December 31, 2015. We conducted a retrospective hospital-based case record review of all patients admitted to one referral hospital in Manila who received a clinical diagnosis of rabies. During the 10-year study period there were 575 patients (average 57.5 cases per year, range 57 to 119) with a final diagnosis of rabies. Most patients were male (n = 404, 70.3%) and aged ≥ 20 years (n = 433, 75.3%). Patients mostly came from the National Capital Region (n = 160, 28.0%) and the adjacent Regions III (n = 197, 34.4%) and IV-A (n = 168, 29.4%). Case mapping and heatmaps showed that human rabies cases were continuously observed in similar areas throughout the study period. Most patients had hydrophobia (n = 444, 95.5%) and/or aerophobia (n = 432, 93.3%). The leading causative animals were dogs (n = 421, 96.3%) and cats (n = 16, 3.7%). Among 437 patients with animal exposure history, only 42 (9.6%) had been administered at least one rabies vaccine. Two patients (0.5%), young children bitten on their face, had received and a full course of rabies vaccine. Human rabies patients were continuously admitted to the hospital, with no notable decline over the study period. The geographical area in which human rabies cases commonly occurred also did not change. Few patients received PEP and there were two suspected cases of PEP failure. The retrospective design of this study was a limitation; thus, prospective studies are required.

Measles outbreak in the Philippines: epidemiological and clinical characteristics of hospitalized children, 2016-2019.

BACKGROUND: Measles outbreaks increased worldwide during 2017-19. The largest outbreak in the World Health Organisation Western Pacific region occurred in the Philippines where first-dose measles-containing vaccine (MCV1) coverage had reduced to 75% in 2018. The aim of this study was to summarise paediatric measles admissions to the national infectious diseases referral hospital in Manila during 2016 to 2019. METHODS: A retrospective single-centre observational study including 5,562 children aged under five years admitted with measles from January 2016 to December 2019. We summarised sociodemographic and clinical characteristics, vaccine status, reported exposures, and outcomes. Univariable and multivariable logistic regression analyses were undertaken to assess associations between different characteristics of hospitalised children and death. FINDINGS: The median age of children hospitalised with measles was 11 months (interquartile range: 7-28). 84·5% of cases were reported not to have received any MCV. The risk of mortality was 3·2%, with 41% of deaths occurring among children aged less than 9 months. No children died who had received two MCV. The following characteristics were significantly associated with mortality in the multivariable analysis: age group, residence outside of the national capital region, not having received any MCV, duration between onset of fever and hospital admission of 7-14 days compared with 0-3 days, not receiving vitamin A supplementation, having pneumonia, and gastroenteritis. INTERPRETATION: The Philippines remains at risk of future measles epidemics. Routine immunization needs to be strengthened and earlier timing of MCV1 requires further evaluation to reduce measles incidence and mortality.

Association between Ambient Temperature and Severe Diarrhoea in the National Capital Region, Philippines.

Epidemiological studies have quantified the association between ambient temperature and diarrhoea. However, to our knowledge, no study has quantified the temperature association for severe diarrhoea cases. In this study, we quantified the association between mean temperature and two severe diarrhoea outcomes, which were mortality and hospital admissions accompanied with dehydration and/or co-morbidities. Using a 12-year dataset of three urban districts of the National Capital Region, Philippines, we modelled the non-linear association between weekly temperatures and weekly severe diarrhoea cases using a two-stage time series analysis. We computed the relative risks at the 95th (30.4 °C) and 5th percentiles (25.8 °C) of temperatures using minimum risk temperatures (MRTs) as the reference to quantify the association with high- and low-temperatures, respectively. The shapes of the cumulative associations were generally J-shaped with greater associations towards high temperatures. Mortality risks were found to increase by 53.3% [95% confidence interval (CI): 29.4%; 81.7%)] at 95th percentile of weekly mean temperatures compared with the MRT (28.2 °C). Similarly, the risk of hospitalised severe diarrhoea increased by 27.1% (95% CI: 0.7%; 60.4%) at 95th percentile in mean weekly temperatures compared with the MRT (28.6 °C). With the increased risk of severe diarrhoea cases under high ambient temperature, there may be a need to strengthen primary healthcare services and sustain the improvements made in water, sanitation, and hygiene, particularly in poor communities.

Diphtheria in Metro Manila, the Philippines 2006-2017: A Clinical, Molecular, and Spatial Characterization.

BACKGROUND: Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. METHODS: We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). RESULTS: We studied 267 patients (range:12-54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8-50.0%). A higher number of cases and CFR was observed among children <10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types. CONCLUSIONS: Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized.

Correction to: Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines.

[This corrects the article DOI: 10.1186/s41182-020-00241-8.].

Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to almost every region and country in the world, leading to widespread travel restrictions and national lockdowns. Currently, there are limited epidemiological and clinical data on COVID-19 patients from low and middle-income countries. We conducted a retrospective single-center study of the first 100 individuals with suspected COVID-19 (between Jan. 25 and Mar. 29, 2020) admitted to San Lazaro Hospital (SLH), the national infectious diseases referral hospital in Manila, Philippines. RESULTS: Demographic data, travel history, clinical features, and outcomes were summarized and compared between COVID-19 confirmed and non-confirmed cases. The first two confirmed cases were Chinese nationals, admitted on Jan. 25. The third confirmed case was a Filipino, admitted on Mar. 8. Trends toward confirmed COVID-19 cases not reporting international travel and being admitted to SLH from the densely populated area of Manila city were observed during Mar. 8-29. All 42 of the 100 confirmed COVID-19 cases were adults, 40% were aged 60 years and above and 55% were male. Three were health workers. Among individuals with suspected COVID-19, confirmed cases were more likely to be older, Filipino, not report international travel history and have at least one underlying disease, particularly diabetes, report difficulty in breathing, and a longer duration of symptoms. In over 90% of non-COVID-19 cases, the alternative diagnosis was respiratory. Nine (21%) confirmed cases died. The median duration from symptoms onset to death was 11.5 (range: 8-18) days. CONCLUSIONS: Imported COVID-19 cases have reduced but local transmission persists and there is a trend toward cases being admitted to SLH from densely populated areas. This study highlights the difficulty in diagnosing COVID-19 on clinical grounds and the importance of diagnostic capacity in all settings. Difficulty of breathing was the only symptom associated with COVID-19 infection and should alert clinicians to the possibility of COVID-19. Clinical characteristics of confirmed COVID-19 cases and a hospital case fatality rate of 21% are comparable with other settings.

The non-linear and lagged short-term relationship between rainfall and leptospirosis and the intermediate role of floods in the Philippines.

BACKGROUND: Leptospirosis is a worldwide bacterial zoonosis. Outbreaks of leptospirosis after heavy rainfall and flooding have been reported. However, few studies have formally quantified the effect of weather factors on leptospirosis incidence. We estimated the association between rainfall and leptospirosis cases in an urban setting in Manila, the Philippines, and examined the potential intermediate role of floods in this association. METHODS/PRINCIPAL FINDINGS: Relationships between rainfall and the weekly number of hospital admissions due to leptospirosis from 2001 to 2012 were analyzed using a distributed lag non-linear model in a quasi-Poisson regression framework, controlling for seasonally varying factors other than rainfall. The role of floods on the rainfall-leptospirosis relationship was examined using an indicator. We reported relative risks (RRs) by rainfall category based on the flood warning system in the country. The risk of post-rainfall leptospirosis peaked at a lag of 2 weeks (using 0 cm/week rainfall as the reference) with RRs of 1.30 (95% confidence interval: 0.99-1.70), 1.53 (1.12-2.09), 2.45 (1.80-3.33), 4.61 (3.30-6.43), and 13.77 (9.10-20.82) for light, moderate, heavy, intense and torrential rainfall (at 2, 5, 16, 32 and 63 cm/week), respectively. After adjusting for floods, RRs (at a lag of 2 weeks) decreased at higher rainfall levels suggesting that flood is on the causal pathway between rainfall and leptospirosis. CONCLUSIONS: Rainfall was strongly associated with increased hospital admission for leptospirosis at a lag of 2 weeks, and this association was explained in part by floods.

An evaluation of the safety and potency of equine rabies immunoglobulin through measurement of suppression on vaccine-induced antibody production among healthy volunteers

OBJECTIVE: This study evaluated the safety and potency of a new highly purified equine rabies immunoglobulin (ERIG) through indirect measurement of suppression of vaccine-induced antibody production using rapid fluorescent focus inhibition test.METHODOLOGY: This is a prospective, randomized open labeled clinical study on healthy volunteers. Forty-five subjects were randomly assigned to three groups of 15 subjects: All groups received the purified chick embryo cell culture (PCEC) rabies vaccine using the Zagreb regimen (2-1-1). Group A then received ERIG at the same site where the PCEC vaccine was administered; Group B received ERIG at a distant site from where the PCEC vaccine was administered; Group C received only the PCEC vaccine at the same regimen. Arithmetic mean (AM), standard deviation (SD) and range were used to describe the baseline characteristics. Geometric mean titer (GMT) was calculated on Days 0, 7, 14, 21 and 28. Wilcoxon rank-sum test and Kruskall-Wallis Analysis of Variance test were used to compare the means of two and three groups, respectively. Local and systemic adverse reactions were reported by subjects and monitored by investigators.RESULTS: By day 14, 64% of the subjects in Group A, 20% in Group B and 7.0% in Group C failed to seroconvert. During that same period, comparative analysis of GMT of Group A (0.36, 95% CI: -17.92 to 18.64), Group B (1.09, 95% CI: 0.14 to 2.04) and Group C (3.90, 95% CI: -0.63 to 8.43) showed statistically significant differences (p = 0.0016). In terms of safety, neither serious adverse events nor anaphylactic reactions were reported.CONCLUSION: ERIG is a potent and safe product that can be effectively used for passive immunization in category III rabies exposures. In resource-limited areas, this product is an excellent alternative to human rabies immunoglobulin (HRIG).