Recombinomics Commentary Detained hospital fevers QENA both happy Rizq “28 years” of the Naga village of solar modules and David Nasser Zaghloul Khulud “4 years” of the Naga village of Duma Mahrousa and Muhammad Arif Mahmood, “years and 4 months” from the village of Dandara, Nabil Abdalenaim Alhawwal “8 years” from the village of solar modules on suspicion of contracting bird flu virus.

QENA detained in hospital diets 5 people suspected of contracting the disease are: Omaima Fatehy «41 years», housewife, and her baby Ahmed Yacoub, two, and Zeinab Mahmoud Alhenwany «40 years», housewife, and Suad Abdullah Hamid, «40 years», and the Princess Razeq Abulhasan, «21 years», housewife, on suspicion of having bird flu

In Qena, the Directorate of Health announced a state of emergency in a hospital after the fever in the central laboratories of the Ministry of Health wounded girl, “Israa Saad Shafi,” which showed symptoms of the disease last Monday and was taken to the hospital.

Detained hospital fevers QENA woman on suspicion of being infected with bird flu, which entered the El-Shafei Bkhittp (48 years old), a housewife from the village of Qena, the status of solar modules, in a very weak condition,

The above translations describe some of the patients hospitalized in Qena recently.  It is unlikely that these patients will be confirmed, because less than 1% of patients hospitalized with bird flu symptoms and stated contact with dead or dying poultry are confirmed.  This low confirmation rate leads to a lack of correspondence between suspect hospitalized patients described in media reports and those that are confirmed, because even if 10% of the hospitalized patients are covered in media reports, it is likely that the suspect cases will be the 99% of patients who test negative.

However, the survival of all confirmed cases this year and the concentration of cases among toddlers (10/12 confirmed cases) has raised concerns that the number of H5N1 infections in Egypt is markedly higher than the number of confirmed cases, and a significant number of the hospitalized patients produce false negatives in the PCR testing done to determine which patients eventually are confirmed.  

These concerns have been heightened further because of two cousins who are next door neighbors and developed bird flu symptoms four days apart, signaling human to human transmission between the toddlers.  Moreover, there have been no confirmed H5N1 poultry cases in the Beheira neighborhood of the two toddlers, and the toddler confirmed prior to the cousins in Beheira was in Qena, where there has also been no confirmed poultry cases.  

The confirmation of H5N1 in toddlers that are not linked to confirmed poultry cases raises concerns of silent transmission among symptomatic patients that had relatively mild cases or respond to oseltamivir treatment, which is given to suspect patients prior to test results.

The analysis of clusters provides insight into potential false negatives.  The largest confirmed cluster to date in Egypt was in Gharbiya in late 2006.  Three family members were fatally infected, but only two were PCR positive, demonstrating that even symptomatic fatal cases could test negative on PCR testing.

Similar concerns were generated when NAMRU-3 investigated a cluster in Pakistan.  Only one family member was PCR positive.  He died, as did a brother who was not tested.  However, the index case, who survived but developed pneumonia , tested negative in the PCR test, yet was found to have an H5N1 titer of 2560, a very high number.  Moreover, another brother who survived had an H5N1 titer of 320, again giving a clear signal of H5N1 infection by the first brother to die. Moreover, a fifth brother, who was asymptomatic also tested negative by PCR, but also had a titer of 320.  Thus, of the four brothers who were tested and were clearly infected with H5N1, only one was PCR positive (and that isolate was sequenced and found to be clade 2.2.3).

However, these false negatives are not limited to cases in Egypt or cases tested by NAMRU-3.  The first four suspect siblings in Turkey in late 2006 also initially tested negative in PCR testing of throat swabs, but fluid collected when the first three cases were near death were PCR positive and clade 2.2 sequences were released from two of the siblings.  Moreover, H5N1 was never confirmed in the fourth sibling. Thus, the prior false negatives in clade 2.2 infections, raises concerns of false negatives in clade 2.2 infections in Egypt.  

Therefore, in addition to testing of asymptomatic patients for neutralizing antibodies, the symptomatic patients who were PCR negative but had bird flu symptoms and poultry contacts should be among the first tested for H5N1 antibodies.   Similarly, at risk groups such as toddlers with symptoms but no reported poultry contacts should also be tested by PCR, as well as neutralizing antibodies in convalescent serum collections.

The confirmation of H5N1 in mild cases in toddlers, coupled with the large number of patients hospitalized with bird flu symptoms, should  lead to much more aggressive testing of patients in Egypt.