Infectious Diseases News Brief - February 15, 2013

 

Canada Communicable Disease Report
CCDR Weekly

Extra-couple HIV transmission in sub-Saharan Africa: a mathematical modelling study of survey data

Background
The proportion of heterosexual HIV transmission in sub-Saharan Africa that occurs within cohabiting partnerships, compared with that in single people or extra-couple relationships, is widely debated. The researchers estimated the proportional contribution of different routes of transmission to new HIV infections. As plans to use antiretroviral drugs as a strategy for population-level prevention progress, understanding the importance of different transmission routes is crucial to target intervention efforts.

Methods
The researchers built a mechanistic model of HIV transmission with data from Demographic and Health Surveys (DHS) for 2003—2011, of 27,201 cohabiting couples (men aged 15—59 years and women aged 15—49 years) from 18 sub-Saharan African countries with information about relationship duration, age at sexual debut, and HIV serostatus. The researchers combined this model with estimates of HIV survival times and country-specific estimates of HIV prevalence and coverage of antiretroviral therapy (ART). The researchers then estimated the proportion of recorded infections in surveyed cohabiting couples that occurred before couple formation, between couple members, and because of extra-couple intercourse.

Findings
In surveyed couples, the researchers estimated that extra-couple transmission accounted for 27—61% of all HIV infections in men and 21—51% of all those in women, with ranges showing intercountry variation. The researchers estimated that in 2011, extra-couple transmission accounted for 32—65% of new incident HIV infections in men in cohabiting couples, and 10—47% of new infections in women in such couples. Their findings suggest that transmission within couples occurs largely from men to women; however, the latter sex have a very high-risk period before couple formation.

Interpretation
Because of the large contribution of extra-couple transmission to new HIV infections, interventions for HIV prevention should target the general sexually active population and not only serodiscordant couples.

Source: Extra-couple HIV transmission in sub-Saharan Africa: a mathematical modelling study of survey data

Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial

Background
BCG vaccination provides incomplete protection against tuberculosis in infants. A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG. The researchers aimed to assess safety, immunogenicity, and efficacy of MVA85A against tuberculosis and Mycobacterium tuberculosis infection in infants.

Methods
In their double-blind, randomised, placebo-controlled phase 2b trial, the researchers enrolled healthy infants (aged 4—6 months) without HIV infection who had previously received BCG vaccination. The researchers randomly allocated infants (1:1), according to an independently generated sequence with block sizes of four, to receive one intradermal dose of MVA85A or an equal volume of Candida skin test antigen as placebo at a clinical facility in a rural region near Cape Town, South Africa. The researchers actively followed up infants every 3 months for up to 37 months. The primary study outcome was safety (incidence of adverse and serious adverse events) in all vaccinated participants, but the researchers also assessed efficacy in a protocol-defined group of participants who received at least one dose of allocated vaccine. The primary efficacy endpoint was incident tuberculosis incorporating microbiological, radiological, and clinical criteria, and the secondary efficacy endpoint was M tuberculosis infection according to QuantiFERON TB Gold In-tube conversion (Cellestis, Australia).

Findings
Between July 15, 2009, and May 4, 2011, the researchers enrolled 2797 infants (1399 allocated MVA85A and 1398 allocated placebo). Median follow-up in the per-protocol population was 24·6 months (IQR 19·2—28·1), and did not differ between groups. More infants who received MVA85A than controls had at least one local adverse event (1251 [89%] of 1399 MVA85A recipients and 628 [45%] of 1396 controls who received the allocated intervention) but the numbers of infants with systemic adverse events (1120 [80%] and 1059 [76%]) or serious adverse events (257 [18%] and 258 (18%) did not differ between groups. None of the 648 serious adverse events in these 515 infants was related to MVA85A. 32 (2%) of 1399 MVA85A recipients met the primary efficacy endpoint (tuberculosis incidence of 1·15 per 100 person-years [95% CI 0·79 to 1·62]; with conversion in 178 [13%] of 1398 infants [95% CI 11·0 to 14·6]) as did 39 (3%) of 1395 controls (1·39 per 100 person-years [1·00 to 1·91]; with conversion in 171 [12%] of 1394 infants [10·6 to 14·1]). Efficacy against tuberculosis was 17·3% (95% CI −31·9 to 48·2) and against M tuberculosis infection was −3·8% (—28·1 to 15·9).

Interpretation
MVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need exploration.

Source: Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial

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