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|        | s |   |                                                          |
|        | w |   |                                                          |
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|        | . |   |                                                          |
+--------+---+---+----------------------------------------------------------+
| **Sp   |   |   | After a measles mass vaccination campaign that targets   |
| ecific |   |   | children 9 months to 14 years of age:                    |
| a      |   |   |                                                          |
| ims:** |   |   | 1.  Determine the rate of adverse events following       |
|        |   |   |     immunization (AEFI) suspected and proven to be       |
|        |   |   |     related to measles vaccine such as fever, rash,      |
|        |   |   |     thrombocytopenia, pneumonitis, anaphylaxis and       |
|        |   |   |     encephalitis in children with and without HIV        |
|        |   |   |     infection.                                           |
|        |   |   |                                                          |
|        |   |   | 2.  Determine if any severe adverse event is related to  |
|        |   |   |     infection with measles vaccine virus through viral   |
|        |   |   |     culture / PCR and RNA sequencing.                    |
|        |   |   |                                                          |
|        |   |   | 3.  Determine the rate of morbidity due to pneumonia,    |
|        |   |   |     diarrheal disease, thrombocytopenia and CNS disease  |
|        |   |   |     and the rate of mortality during a 1 month period    |
|        |   |   |     before and a 12 month period after the campaign in   |
|        |   |   |     children with and without HIV infection.             |
+--------+---+---+----------------------------------------------------------+
| **B    |   |   | Little information exists on the risk of adverse events  |
| ackgro |   |   | following measles immunization among persons with HIV    |
| und:** |   |   | infection or in populations with high rates of HIV       |
|        |   |   | infection. Several authors have reported the results of  |
|        |   |   | vaccinating small groups of children and adults with HIV |
|        |   |   | against measles, either as a primary or secondary        |
|        |   |   | vaccination, with only two serious or unexpected adverse |
|        |   |   | events reported among the 365 vaccine recipients. \[1\]  |
|        |   |   | These events were clinical measles with in addition      |
|        |   |   | conjunctivitis in one case \[2\] and diarrhea in         |
|        |   |   | another. \[3\]                                           |
|        |   |   |                                                          |
|        |   |   | In addition, several case reports have documented severe |
|        |   |   | adverse events following measles vaccination in          |
|        |   |   | immunocompromised people, \[4-10\] including one young   |
|        |   |   | adult with HIV. \[11\] Most events have been             |
|        |   |   | encephalitis or pneumonitis and led to death in six of   |
|        |   |   | the eight case reports. Measles vaccine virus was        |
|        |   |   | confirmed in three of the cases, including the one       |
|        |   |   | occurring in the adult with HIV. These adverse events    |
|        |   |   | have occurred after intervals of several months after    |
|        |   |   | vaccination, compared to 2 -- 3 weeks in adverse events  |
|        |   |   | occurring in people without HIV.                         |
|        |   |   |                                                          |
|        |   |   | A complicating factor in the detection of adverse events |
|        |   |   | after measles vaccination is the baseline high morbidity |
|        |   |   | and mortality of children living with HIV in Africa,     |
|        |   |   | based on reports describing the morbidity and mortality  |
|        |   |   | of African cohorts of HIV-infected children. \[12-17\]   |
|        |   |   | In a cohort of 1000 HIV-infected children, followed over |
|        |   |   | the course of a year, not receiving anti-HIV medications |
|        |   |   | and not vaccinated against measles, we would expect 2.4  |
|        |   |   | episodes of diarrhea per child per year (2400 episodes   |
|        |   |   | total), 1.08 episodes of pneumonia (1080 episodes        |
|        |   |   | total), 3.84 clinic visits (3840 for all children), and  |
|        |   |   | 0.49 hospitalizations (490 for all children). In the     |
|        |   |   | HIV-negative children, the rates of episodes per year    |
|        |   |   | per child would be 1.45 for diarrhea, 0.43 for           |
|        |   |   | pneumonia, 2.72 for clinic visits, and 0.17 for          |
|        |   |   | hospitalizations. During follow-up, based on data        |
|        |   |   | collected in Malawi, 340 HIV-infected children would be  |
|        |   |   | expected to die, 225 from pneumonia and 115 from         |
|        |   |   | diarrhea as compared to only 36 deaths in HIV-negative   |
|        |   |   | children. \[16\] Please see Annex 2 for additional       |
|        |   |   | information. These are rough approximations given that   |
|        |   |   | the data are from children younger than might            |
|        |   |   | participate in the vaccination campaign, though most     |
|        |   |   | children in the clinics are likely to be under 5 years   |
|        |   |   | of age.                                                  |
+--------+---+---+----------------------------------------------------------+
| *      |   | T |                                                          |
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|        |   | : |                                                          |
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|        |   | 2 |                                                          |
|        |   | . |                                                          |
+--------+---+---+----------------------------------------------------------+

**Annex 1. References**

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immunodeficiency virus epidemic for control and eradication of measles.
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2\. Sprauer MA, Markowitz LE, Nicholson JK, et al. Response of human
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6\. Mihatsch MJ, Ohnacker H, Just M and Nars PW. Lethal measles giant
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8\. Monafo WJ, Haslam DB, Roberts RL, Zaki SR, Bellini WJ and Coffin CM.
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10\. Valmari P, Lanning M, Tuokko H and Kouvalainen K. Measles virus in
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11\. Angel JB, Walpita P, Lerch RA, et al. Vaccine-associated measles
pneumonitis in an adult with AIDS. Ann Intern Med 1998;129:104-6

12\. Fawzi WW, Msamanga GI, Wei R, et al. Effect of providing vitamin
supplements to human immunodeficiency virus-infected, lactating mothers
on the child\'s morbidity and CD4+ cell counts. Clin Infect Dis
2003;36:1053-62

13\. Marum LH, Bagenda D, Guay L, et al. Three-year mortality in a
cohort of HIV-1 infected and uninfected Ugandan children. In: XI
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14\. Mbori-Ngacha D, Nduati R, John G, et al. Morbidity and mortality in
breastfed and formula-fed infants of HIV-1- infected women: A randomized
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15\. Spira R, Lepage P, Msellati P, et al. Natural history of human
immunodeficiency virus type 1 infection in children: a five-year
prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study
Group. Pediatrics 1999;104:e56

16\. Taha TE, Kumwenda NI, Broadhead RL, et al. Mortality after the
first year of life among human immunodeficiency virus type 1-infected
and uninfected children. Pediatr Infect Dis J 1999;18:689-94.

17\. Taha TE, Graham SM, Kumwenda NI, et al. Morbidity among human
immunodeficiency virus-1-infected and -uninfected Afric. Pediatrics
2000;106:e77

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