article: In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities. We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the neighborhoods where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64. 6% (529/819) were from Maputo City. Dogs were responsible for 97. 8% (801/819) of all animal bites, but only 27. 0% (126/467) were immunized. Factors significantly associated with human rabies were: age <15 years (p = 0. 05), bite by stray dog (p = 0. 002), deep wound (p = 0. 02), bite in the head (p = 0. 001), bite by unimmunized dog (p = 0. 01), no use of soap and water (p = 0. 001), and no post-exposure prophylaxis (p = 0. 01). Implementation of control measures for rabies is poor in Maputo and Matola cities, where cases of human rabies were strongly associated with bites by stray and unvaccinated dogs and irregular implementation of post-exposure measures.
  Rabies is a zoonotic viral disease, belonging to the Lyssavirus genus of the Rhabdoviridae family, which infects mammals and causes fatal encephalitis [1,2]. A bite by a rabid dog represents the source of infection in more than 99% of cases [3,4]. Almost half of cases occur in children under the age of 15 years [3,5, 6]. In humans, the incubation period of rabies is highly variable, ranging from days to years, with an average of 2–3 months, being influenced by: i) location, extent and depth of the wound; ii) distance between the location of the wound and the central nervous system; iii) concentration of inoculated virus particles and iv) virus strain [1,6, 7]. The incubation period in children tends to be of shorter duration than adults [7]. Although rabies is preventable, and effective control measures are available, the number of deaths is still high and an estimated 59,000 people die from rabies each year in the world, with Asia and sub-Saharan Africa accounting for more than 95% of these deaths [8]. More than 3. 3 billion people are at risk of infection by the rabies virus [3]. Rabies disproportionally affects the poorest and under-resourced populations living in low and middle income countries, and its incidence is on the rise in several countries (8–15). In addition to its negative impact on mortality, rabies also causes a negative economic impact in already impoverished populations (8,16). Lack of reliable data on the burden and risk factors associated with human rabies represents a critical challenge for the formulation of policies and strategies to control the disease and has been considered a major cause for the under investment in rabies control measures in these countries (8,20). With regard to Mozambique, recent estimates of the burden of rabies in sub-Saharan Africa ranked Mozambique as one of the countries with the highest burden [8]. In Mozambique, rabies remains badly neglected. Mozambique elaborated a national rabies control strategy in 2010 (9). Control activities and responsibilities are shared by the Ministry of Agriculture, Ministry of Health, Municipalities (city governments) and local authorities. The main interventions are: i) immunization of domestic pets, mostly dogs; ii) removal and euthanizing of all stray and unowned dogs and iii) timely and appropriate implementation of post-exposure prophylaxis, including washing of the bite site and post-exposure vaccination (1,6). Veterinary immunization is mostly provided by the Public Veterinary Services in coordination with the local municipalities; private veterinary services also provide vaccination, but on a limited scale. The municipalities are also responsible for the removal of stray dogs (21). Post-exposure vaccination and rabies immunoglobulin (RIG) are offered at specialized prevention facilities, named Prophylaxis Centers, which are scattered throughout the country (21). All victims of animal bites are referred to these centers for five doses of prophylactic inactivated rabies vaccine produced in cell culture, and RIG, as per the WHO protocol. Conduct regarding the animal follows national and international procedures. Owners are advised to quarantine all biting animals in the household for ten days and to return to the center if the animal develops any sign of rabies (1,6). At ten days they must return to the center for a physical examination of the animal by a health professional (1,21,36). However, in Mozambique, as in many sub-Saharan Africa countries, these procedures are conducted irregularly, resulting in frequent cases or outbreaks of rabies. In Maputo City, the national capital, health authorities were alerted to a possible outbreak of rabies in July 2014 when Maputo Central Hospital admitted several patients with rabies in a short time period. This outbreak prompted further investigation of both rabies cases and animal bites in the city and adjoining Matola City, capital of Maputo Province. To our knowledge this represents the first ever attempt to investigate a rabies outbreak and determine the epidemiological profile of animal bites in Mozambique. We aimed to determine the clinical and epidemiological features of human rabies cases detected during the outbreak, the risk factors for developing rabies, and the epidemiological features of animal bites in Maputo and Matola cities We expect that the findings of this study will contribute to formulating appropriate recommendations and strategies to control rabies in Mozambique.
  A rabies outbreak is a public health emergency and this investigation was part of the public health response. For this reason, no protocol was submitted to local IRB and the investigation was exempt from ethical approval, but permission to conduct the investigation was obtained from local health authorities and local community leaders. In addition, the investigation team ensured that a comprehensive explanation of the investigation was provided to all health professionals and other participants. A verbal consent was obtained from each participant or their parents and/or legal guardians before the interview and also to use their questionnaire forms. Maputo City is the capital of Mozambique, with an area of 347 km2 and a population estimated at 1,225,868 inhabitants [9]. The city is divided into seven districts, which are in turn divided into 61 neighborhoods. An estimated 70% of inhabitants live in the suburbs, often in overcrowded housing with poor sanitation and a low education level. A small proportion live in the central urban (13. 8%) and peri-urban (8. 7%) areas [9]. Matola City, the capital of Maputo Province, adjoins Maputo City, and has an area of 373 km2 and a population estimated at 893,000 inhabitants [9]. Matola City is divided into 3 administrative posts and 42 neighborhoods. Although the vast majority of the population lives in peri-urban or semi-rural areas, the city has a rapid growth rate and is rapidly urbanizing. Maputo and Matola cities have several Prophylaxis Centers, to which all animal bites are referred. Both cities are situated in the southern part of the country (Fig 1). Notifications of rabies cases in Maputo City increased from one in 2013 to 21 in 2014 (22). The incidence of notified cases of dog bites per inhabitant in Maputo City is the highest in the country (17). Immediately after the notification of the outbreak, the following control measures were instituted: i) establishment of a coordination committee comprising the National Veterinary Services in the Ministry of Agriculture, National Institute of Health and the National Directorate for Public Health in the Ministry of Health, Maputo City Council, Maputo Province government and local communities; ii) affixing posters in health units regarding treatment of animal bites and post- exposure prophylaxis; iii) delivery of additional quantities of anti-rabies vaccine to the Prophylaxis Centers in Maputo City and Province to ensure an adequate stock; iv) decentralization of post-exposure prophylaxis to Matola 2 and Boane health centers; v) vaccination of dogs in the neighborhoods where human rabies cases had occurred; vi) mass vaccination campaign of dogs in Maputo City and Maputo Province; vii) Participation of private veterinary clinics in animal vaccination; viii) collection of stray dogs in selected neighborhoods; ix) community education regarding prevention and control measures. All forms were anonymized. Data were analyzed using the statistics package STATA 12. 1 (College Station, Texas: Stata Corp, USA, 2012). Frequencies, proportions, odds ratio (OR) and chi-square test were calculated for categorical variables. Median, interquartile range (IQR) and Mann-Whitney test were calculated for numerical variables. A p-value <0. 05 was considered statistically significant. Logistic regression analysis was used to determine the variables independently associated with human rabies, controlling for confounders. The analysis was built using backwards stepwise method and Log Likelihood Ratio Test. For this purpose, all variables with a p- value less than 0. 25 on univariate analysis were included in the initial multivariate model. A p-value < 0. 05 was considered of statistical significance in the final model.
  We detected a total of 12 cases of fatal rabies admitted to Maputo Central Hospital during the period between April and July 2014. These were comprised of the initial three cases, a further three cases admitted later, and a further six cases identified by retrospective analysis of the medical records. During the community investigation, an additional two cases admitted in August to a different hospital in Maputo were identified. Rabies was not suspected and for this reason, they were not initially recorded as rabies. We have included them in the analysis. Table 1 shows that, of the 14 cases of human rabies, 12 were children below 15 years of age and 8 were male. Ten lived in the suburban areas of Maputo City, 3 in Matola City and 1 in Boane District, a rural district in Maputo Province (Fig 1). Half of the deaths occurred between 11th June and 13th July (epidemiological weeks 24 to 28), as shown in Fig 2. All of the 14 cases of human rabies involved dog bite. Only one of the dogs had been immunized. The average duration of hospitalization before death was two days, ranging between less than 24 hours up to 5 days, as shown in Table 1. Main clinical findings before death were excited behavior (100%), mental disturbance (78. 6%), visual hallucinations (71. 4%) and hypersalivation (71. 4%), as shown in Fig 3. No rabies victim received full post-exposure vaccination. In Matola, one victim attended a health center and received only tetanus vaccine and the parents were informed that it was sufficient. Three victims attended the Prophylaxis Center in Matola and the parents were told that there was no vaccine available. In Maputo City, of ten victims who attended health centers, nine were given only tetanus vaccine and parents were told that it was sufficient. They were not referred to the Prophylaxis Center. The one case who was referred was only given two doses of vaccine. A total of 819 cases of animal bites were registered during the period under investigation (April to July 2014), 529 (64. 6%) in Maputo City and 290 (35. 4%) in Matola City, as shown in Table 2. Fig 1 shows that cases came from many different neighborhoods. Fig 2 shows that the number of bites ranged from 32 to 58 cases per week. Table 2 also shows that 57. 3% (469/819) of bite victims were male. The median age of victims was 20 years (IQR: 10–34 years), ranging between 1 and 86 years. Children under 15 years of age comprised 37. 9% (310/819) of the victims. In both cities, the majority of animal bites occurred in people living in the suburbs (85. 1%; 697/819), with only 14. 9% (122/819) living in the central urban area. Most animal bites were caused by dogs (97. 8%, 801/819). Small proportions were attributed to cats (1. 1%, 9/819), humans (1. 0%, 8/819) and mice (0. 1%, 1/819). Only 72 (8. 7%) of animal bite victims had an animal bite investigation form filled out and the majority of these forms were incomplete. Most of the information was, therefore, retrieved from the logbooks. Information on post-exposure vaccination was available in only 19. 0% (156/819) of victims, of whom 7. 7% (12/156) were from Maputo City and 92. 3% (144/154) from Matola City. Of the 156 victims for whom information on post-exposure vaccination was available, only 47 (30. 1%) received the vaccine, of whom all except one lived in Matola City. The biting dog was known or owned in 58. 3% (467/801) of dog bite cases. In 23. 7% (194/801) and 17. 1% (140/801) the biting dog was stray or unknown, respectively. Of the 467 dogs that were owned, only 7. 3% (34/467) of the owners provided any information on the clinical condition of the animal 10 days after the bite. Of the total known or owned dogs, 4. 3% (20/467) were still alive, 1. 1% (5/467) had died a natural death and 0. 6% (3/467) were killed. Of the 467 dog that were known or owned, 27. 0% (126/467) were immunized, 23. 0% (108/467) were not immunized and for the remaining 50% (233/467) their immunization status was unknown. Among those that were immunized, 92. 1% (116/126) had a valid immunization status and in 7. 9% (10/126) vaccine validity had expired. During the community investigation, we were able to link seven cases of human rabies to bites of five dogs, as shown in Fig 4. Four of the five dogs were each linked to one rabies victim, and one was linked to three victims, two of whom were identified in the community investigation. Fig 4 also shows that six other people were bitten by four of these rabid dogs, but did not develop rabies. Of these six cases, only one received post-exposure vaccination and none received RIG. Also, one rabid child had bitten his mother, but she did not develop rabies. Data collected from the Central Veterinary Laboratory in Maputo showed laboratory confirmed rabies in two dogs during the period under investigation. Demographic variables and other known risk factors were compared between cases of animal bites and cases of human rabies in order to determine the predictive variables associated with a higher risk of developing rabies after an animal bite (Table 3). Age < 15 years (OR: 4. 8, p = 0. 05), a bite by a stray dog (OR: 13. 6, p = 0. 00), deep wound (OR: 6. 1, p = 0. 02), bite in the head (OR: 11. 6; p = 0. 00), bite by an unvaccinated dog (OR: 16. 7, p = 0. 01), failure to wash the bite site with soap and water (OR: 17. 1, p = 0. 00) and no post-exposure prophylaxis (OR: 16. 7, p = 0. 01), were all associated with the development of rabies.
  A major limitation of our study was the poor quality of records of cases of animal bites at the Prophylaxis Centers.
  In conclusion, our study shows that weak control measures, including low coverage rates of dog immunization, poor control of stray and unowned dogs, inadequate management of bites, and poor availability of and adherence to post-exposure prophylaxis, are major factors driving rabies outbreaks in Maputo and Matola cities. None of the cases of human rabies that occurred during the outbreak were notified through the routine surveillance system, showing that rabies is seriously under-reported. Overall, we recommend aggressive interventions that include regular canine mass vaccination campaigns, improvement of the provision of vaccines to humans and animals, accompanied by regular campaigns to remove stray dogs and massive education in communities and primary schools.
summary: Rabies is a deadly neglected virus that causes an estimated 59,000 deaths each year worldwide. In 2014, an outbreak of human rabies in adjacent Maputo and Matola cities prompted us to investigate the epidemiology and risk factors of human rabies and animal bites in the two cities. We reviewed cases of human rabies and animal bites through both health facility and community investigations and carried out a case control study in affected neighborhoods. We found a total of 14 unreported human rabies cases in a four month period, and 819 cases of animal bites in a three month retrospective review of records. Dogs were responsible for all rabid bites and for 97. 8% of animal bites. None of the rabid dogs had been vaccinated. Factors significantly associated with human rabies were: age <15 years, bite by a stray dog, deep wound, bite in the head, bite by an unimmunized dog, failure to use soap and water to cleanse the wound, and to vaccinate after the bite. We concluded that the poor implementation of control measures for rabies had led to the outbreak and recommended strengthening implementation, particularly in rapidly urbanizing areas.
keywords: medicine and health sciences
  pathology and laboratory medicine
  pathogens
  immunology
  tropical diseases
  geographical locations
  vertebrates
  microbiology
  dogs
  animals
  mammals
  veterinary hospitals
  viruses
  preventive medicine
  vaccines
  rabies
  rna viruses
  neglected tropical diseases
  infectious disease control
  vaccination and immunization
  africa
  veterinary science
  veterinary medicine
  rabies virus
  public and occupational health
  infectious diseases
  veterinary diseases
  zoonoses
  medical microbiology
  microbial pathogens
  people and places
  mozambique
  lyssavirus
  viral pathogens
  biology and life sciences
  viral diseases
  amniotes
  organisms
title: Epidemiology, clinical features and risk factors for human rabies and animal bites during an outbreak of rabies in Maputo and Matola cities, Mozambique, 2014: Implications for public health interventions for rabies control