2 Quarter 2017 Compiled by Dr S Miller & Dr L Maree

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NEWSLETTER

MEASLES

There have been an unexpectedly large number of measles cases in Gauteng recently. This newsletter is intended to highlight the epidemiology, clinical manifestations, diagnosis and prevention of this disease.

Measles is a highly contagious viral illness. It occurs worldwide and is attended by significant morbidity and mortality. Because humans are the only reservoir of the virus, eradication of measles should be possible. This goal, however, has not been achieved.

EpidemiologyIn the pre-vaccine era, more than 90% of children acquired measles by the age of 15 years. There were approximately 2 million deaths annually, the majority occurring in children < 5 years of age. Following the availability of measles vaccination in the 1960s there was a steep decline in the numbers of cases with a concomitant reduction in mortality.

Despite the near universal availability of measles vaccine, certain individuals remain at risk for infection. They include infants too young to be vaccinated, those who have not been vaccinated, those who have not received a second dose of measles vaccine, people in whom vaccination failed to elicit protective immunity (a very rare event), and adults with waning immunity despite being immunised in childhood.

TransmissionMeasles is highly contagious with an attack rate approaching 90%. Transmission occurs via aerosol droplets and respiratory secretions from an infected person. Aerosol droplets containing viable virus can remain in suspension in the air for up to two hours.

The median incubation period for measles is 14 days (6 � 19 days). An infected individual is contagious from 4 days prior to the appearance of the rash, and for approximately 4 days thereafter. The late prodromal stage, when the individual is febrile and has respiratory symptoms, is thought to be the most contagious period.

Clinical manifestationsTypically, measles virus infection has four stages: incubation, prodrome, exanthem and recovery. Individuals are usually asymptomatic during the incubation stage despite infection of regional lymph nodes followed by viraemia and spread to the reticuloendothelial system.A second viraemia heralds the appearance of symptoms and the onset of the prodromal phase. They include fever, malaise, and anorexia followed by conjunctivitis, coryza and cough. Generally the prodromal symptoms progressively intensify and, shortly before the onset ofthe exanthem, Koplik's spots appear. These are white, grey or blueish elevations with an erythematous base that typically occur on the buccal mucosa opposite the molar teeth. When present, Koplik's spots are pathognomonic of measles. Two to three days thereafter the rash appears.

Measles rash is erythematous, maculopapular and initially blanches on pressure. It classically begins on the face and spreads downwards to involve the rest of the body, including the palms and soles. The rash may become petechial and, in severe cases, haemorrhagic. In children the extent and confluence of the rash usually correlates with the severity of the illness. Concomitant manifestations include lymphadenopathy, high fever, significant respiratory signs including pharyngitis and non-purulent conjunctivitis. The rash usually begins to resolve after 2 � 3 days. In lighter-skinned people darkening of the lesions to a dark brown colour can be easily observed; thereafter the rash fades followed by desquamation (usually sparing the palms and soles). The duration of the rash is approximately 7 days with lesions resolving in the order in which they appeared.

thCough may persist for one or two weeks after measles. Fever invariably resolves by the 4 day after the appearance of the rash. Persistence of fever beyond this time suggests a measles-related complication. Measles infection causes transient depression of cell mediated immunity. This may result in secondary bacterialand other viral illnesses including pneumonia and diarrhoea. In addition, reactivation of tuberculosis may occur. Following recovery, immunity is thought to be lifelong. Cases have been described, however, of waning immunity in adulthood with a risk of re-infection.

ComplicationsComplications occur in up to 30% of measles cases. Risk factors for complications include age < 5 years, malnutrition, underlying immunodeficiency and pregnancy. Diarrhoea is the most common complication, and otitis media is also frequently encountered. Keratitis leading to blindness (especially in patients with vitamin A deficiency), and corneal ulceration can occur, as well as myocarditis and pericarditis. Most deaths are due to respiratory tract disease or acute post-infectious encephalitis. Subacute sclerosing panenencephalitis (SSPE) isa rare, progressive, fatal degenerative disease of the central nervous system that can develop 7 � 10 years after natural measles virus infection.

Measles in pregnancyMeasles during pregnancy is associated with an increased risk of maternal and foetal complications. Maternal complications include pneumonia, diarrhoea and encephalitis. Measles infection during pregnancy is not associated with congenital abnormalities. The risk for premature delivery of a low birth weight infant, spontaneous miscarriage, intrauterine death and maternal death is however significantly increased.

DiagnosisThe diagnosis of measles should be considered in any patient presenting with a febrile rash illness and clinically compatible symptoms (e.g. cough, coryza, conjunctivitis), especially in the setting of possible or confirmed recent exposure to an individual with a febrile rash. Serology for measles antibody, and PCR for measles virus RNA are the preferred diagnostic tests.

Detection of measles virus-specific IgM in serum is diagnostic of acute infection, in the absence of recent vaccination. Anti-measles IgM is generally detectable three days after the appearance of the rash and persistsfor approximately 4 weeks. Anti-measles IgG becomes detectable from approximately 7 days after onset of therash and persists lifelong. Since both IgG and IgM may be negative on the day that the rash appears, a second sample, taken three days later, may be required to document seroconversion.

Measles virus RNA can be detected in upper respiratory tract secretions (throat swab, nasopharyngeal swab) and in urine for three to four (up to 14) days after appearance of the rash.

NOTE: Measles is a notifiable condition, and any confirmed cases should be reported to the local/provincial surveillance officer. The measles case investigation form must be completed with the relevant clinical information, and the EPID number that was obtained from the surveillance officer, and sent through to the National Institute of Communicable Diseases (NICD). The measles case investigation form is available electronically at: http://nicd.ac.za/assets/files/DOH_Measles_CIF.pdf

TreatmentThe treatment of measles is supportive and includes antipyretics other than aspirin, fluids and treatment of secondary bacterial infections. In the in-patient setting, respiratory precautions should be instituted for four days after the onset of rash.

Vitamin A deficiency contributes to delayed recovery and a higher rate of measles complications. In addition, measles may precipitate vitamin A deficiency.

Vitamin A as part of the management of measles is administered once daily for two days at the following doses:· Infants < 6 months of age: 50 000 IU· Infants 6 � 11 months of age: 100 000 IU· Children � 12 months of age: 200 000 IU

PreventionVaccination has led to the interruption of measles transmission and affords protection to the community by means of herd immunity. Due to the high infectivity of measles, herd immunity must be maintained above 85 � 95% to prevent broad transmission.

In South Africa measles immunisation is part of the Expanded Programme on Immunisation (EPI). In the public sector a monovalent vaccine is administered at 6 and 12 months of age; in the private sector MMR (measles, mumps, rubella vaccine) is administered at 12 and 18 months of age. Seroconversion rates exceed 95% following a two-dose vaccination schedule. Note that any dose given during an outbreak should not countas part of the routine two-dose series. If a routine measles vaccine dose is still required, it should be administered after an interval of at least 28 days.

As vaccine-induced measles antibody develops more rapidly than that following natural infection, measles vaccination can also be used as post-exposure prophylaxis in susceptible individuals if given within 3 days of exposure.

Adverse effects of measles vaccinationFever may develop in up to 15% of vaccine recipients, usually within ten days following immunisation and lasts1 � 2 days. A transient rash occurs in approximately 5% of individuals and is generally attributed to the attenuated vaccine strain of the virus. Febrile seizures are the most commonly reported neurological adverse event after vaccination against measles, but the rate of febrile seizures after vaccination is lower than that following natural infection. Febrile seizures after measles vaccination has also not been associated with the subsequent development of epilepsy. Measles vaccine has not been associated with encephalopathy. Multiplestudies have failed to show an association between MMR vaccination and autism, as well as other chronic diseases.

Contraindications to measles vaccinationPregnant women should not receive monovalent measles vaccine or MMR. Women who have received thesevaccines should be counselled to avoid pregnancy for at least one month thereafter. Measles monovalent vaccine and MMR should not be administered to individuals with primary immunodeficiency, leukaemia, lymphoma and other neoplasms affecting the bone marrow or lymphatic system. Both vaccines are also contraindicated in HIV-infected individuals with a CD4 cell count < 200 cells/�L or CD4 percentage < 15% of total lymphocyte count in children. They should also be withheld for one month after discontinuation or dosagereduction of high-dose corticosteroid therapy.

The administration of immunoglobulin or antibody-containing blood products can blunt or block the host response to certain live-virus vaccines. For children and adolescents the suggested intervals between these products and administration of measles or MMR vaccine are 3 months following administration of intramuscular gamma globulin, 6 months following administration of blood and blood-products, and 11 months following intravenous immunoglobulin.

References1. Centers for Disease Control and Prevention (CDC). Global measles mortality, 2000 � 2008. MMWR 2009; 58: 1321.2. Ogbuano IU, et al. Maternal, fetal and neonatal outcomes associated with measles during pregnancy: Namibia, 2009-2010. Clin Infect Dis 2014: 58:1086.3. World Health Organisation. Measles vaccine: WHO position paper. Available at: http://www.who.int/wer/2009/wer8435.pdf?ua=14. Katz SL, Hinman AR. Summary and conclusions: measles elimination meeting, 16-17 March, 2000. J Infect Dis 2004: 189 suppl 1: S43.5. Redd SC, et al. Comparison of vaccination with measles-mumps-rubella vaccine at 9, 12 and 15 months of age. J Infect Dis 2014; 189: suppl 1: S166.6. McLean HQ, et al. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2013; 62:1. 7. Anjali Jain MD, et al. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism, 2015. JAMA; 313 (15): 1534.8. Kroger AT, Duchin J, Vázquez M. General best practice guidelines for immunization. Best practices guidance of the Advisory Committee on Immunization Practices (ACIP). Available at: www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html.

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