Several Bangladesh Nipah outbreaks resulted from person-to-person transmission. The clearest illustration of person to person NiV transmission occurred during the Faridpur outbreak in 2004 [21
]. Four persons who cared for the index patient--his mother, his son, his aunt and a neighbor--became ill 15–27 days after the index patient first developed illness (). During her hospitalization, the index patient's aunt was cared for by a popular religious leader who lived in a nearby village and who became ill 13 days later. When the religious leader became seriously ill, many of his relatives and members of his religious community visited at his home. Twenty-two persons developed Nipah infection after contact with the religious leader. One of these followers moved to his family's house in an adjacent village to receive care after becoming ill where he was cared for by a friend and two family members. These three caregivers and a rickshaw driver, who helped carry him to the hospital as his condition deteriorated, became ill. Ultimately, the chain of transmission involved 5 generations and affected 34 people [21
] (). Physical contact with an NiV infected patient who later died (OR 13.4, 95% CI 2.0, 89) was the strongest risk factor for developing NiV infection in the outbreak.
Chain of person to person transmission in Nipah outbreak, Faridpur, Bangladesh, 2004.
The transmission pattern in Faridpur is not unique. For example, in Thakurgaon in 2007 six family members and friends who cared for an NiV infected patient developed Nipah infection. Cases were more likely than controls to have been in the same room when the index case was coughing [23
]. In a review of the 122 identified Nipah cases identified in Bangladesh from 2001 through 2007, 62 (51%) developed illness after close contact with another Nipah patient [27
]. A small minority of patients infected with NiV, 9 of 122 recognized cases (7%) transmitted NiV to 62 other persons.
Respiratory secretions appear to be particularly important for person-to-person transmission of NiV. NiV RNA is readily identified in the saliva of infected patients [28
]. Anthropological investigations during the Faridpur outbreak highlighted multiple opportunities for the transfer of NiV contaminated saliva from a sick patient to care providers [37
]. Social norms in Bangladesh require family members to maintain close physical contact during illness. The more severe the illness, the more hands-on care is expected. Family members and friends without formal health care or infection control training provided nearly all the hands on care to Nipah patients both at home and in the hospital [38
]. Care providers during the Faridpur outbreak continued to share eating utensils and drinking glasses with sick patients. Leftovers of food offered to see Nipah patients were commonly distributed to other family members. Family members maintained their regular sleeping arrangements, which often involved sleeping in the same bed with a sick, coughing Nipah patient. There was a particularly strong desire to have close physical contact near the time of death, demonstrated by such behaviors as cradling the patients head on the family member's lap, attempting to give liquids to the patient with a spoon or glass between bouts of coughing, or hugging and kissing the sick patient [37
]. In both the Faridpur outbreak in 2004 and the Thakurgaon outbreak in 2007, persons who were in a room when a Nipah patient was coughing or sneezing were at increased risk of Nipah virus infection [21
]. Across all recognized outbreaks in Bangladesh from 2001 through 2007, Nipah patients with respiratory symptoms were more likely to transmit Nipah [27
The capacity for NiV to spread in hospital settings to both staff and patients, was clearly illustrated in a large outbreak affecting 66 people in Siliguri, India in 2001. The outbreak apparently originated from an unidentified patient admitted to Siliguri District Hospital who transmitted infection to 11 additional patients, all of whom were transferred to other facilities. In two of the facilities, subsequent transmission infected 25 staff and 8 visitors [25
]. However, transmission to health care workers is rarely recognized. Among a cohort of 338 health care workers who cared for Nipah patients at three Malaysian hospitals and reported a combined 89 episodes of Nipah patient blood or body fluid directly contacting their bare skin, 39 splash exposures of blood or body fluid into their eyes, nose or mouth, and 12 needle stick injuries, none developed clinical illness associated with Nipah infection [39
]. Health care workers in Bangladesh have much less direct physical contact with patients than in Western hospitals [38
]. Hands-on care is generally provided by family members and friends. No health care workers in Bangladesh who cared for identified Nipah patients have been identified with illness, though confirmed cases include one physician whose source of infection is unknown. A sero-survey among 105 health care workers who cared for at least one of seven patients admitted with Nipah infection at one hospital in Bangladesh identified two health care workers with serological evidence of NiV infection; however their antibody responses (IgG only, no IgM) and lack of symptoms suggest a previous infection, not recent nosocomial transmission [40
Might person to person transmission be associated with particular strains of NiV that have genetic characteristics that lead to person to person transmission? The closely related strains in Malaysia resulted in less frequent and less severe respiratory disease than observed in Bangladesh and were not associated with frequent person to person transmission. However, the pattern of the outbreaks in Bangladesh and India suggests that person to person transmission is more dependent on the characteristics of the occasional Nipah transmitter than a specific strain. If the NiV strain was central to person to person transmission, then secondary cases of NiV would be more likely to become NiV transmitters, than primary cases (because secondary cases would already have selected for strains predisposed to person to person transmission.) However, in the review of seven years of human Nipah infection in Bangladesh, secondary cases were no more or less likely to become Nipah transmitters than were primary cases [27
]. All persons who transmitted Nipah died, suggesting that late stages of infection, presumably with high virus titers, increases the risk of transmission. Even the pattern in Siliguri, the largest recognized Nipah outbreak from apparent person to person transmission, is consistent with the review of seven years of human Nipah infection in Bangladesh. The unidentified index case in Siliguri District Hospital infected 11 patients, 2 of whom infected an additional 33 patients. The 13 day duration of the outbreak at Medinova Hospital suggests two generation of transmission likely occurred there. Taken together this pattern suggests 4 NiV transmitters propagated human infection across 4 generations. There were 67 cases (66 recognized plus the unidentified index case) 4 of whom (5.9%) became Nipah transmitters, a proportion very close to the 7% recognized in Bangladesh. This suggests that the virus strain responsible for this largest recognized person to person outbreak was not exceptional. Its rate of secondary transmission was similar to other strains circulating in South Asia.