Intense Co-Circulation of Non-Influenza Respiratory Viruses during the First Wave of Pandemic Influenza pH1N1/2009: A Cohort Study in Reunion Island

Objective

The aim of the present study was to weigh up, at the community level, the respective roles played by pandemic Influenza (pH1N1) virus and co-circulating human Non-Influenza Respiratory Viruses (NIRVs) during the first wave of the 2009 pH1N1 pandemic.

Methods

A population-based prospective cohort study was conducted in Reunion Island during the austral winter 2009 (weeks 30–44) that allowed identification of 125 households with at least one member who developed symptoms of Influenza-like illness (ILI). Three consecutive nasal swabs were collected from each household member (443 individuals) on day 0, 3 and 8 post-ILI report and tested for pH1N1 and 15 NIRVs by RT-PCR.

Results

Two successive waves of viral infections were identified: a first wave (W33–37) when pH1N1 was dominant and co-circulated with NIRVs, sharply interrupted by a second wave (W38–44), almost exclusively composed of NIRVs, mainly human Rhinoviruses (hRV) and Coronaviruses (hCoV). Data suggest that some interference may occur between NIRVs and pH1N1 when they co-circulate within the same household, where NIRVs were more likely to infect pH1N1 negative individuals than pH1N1 positive peers (relative risk: 3.13, 95% CI: 1.80–5.46, P<0.001). Viral shedding was significantly shorter (P = 0.035) in patients who were co-infected by pH1N1 and NIRV or by two different NIRVs compared to those who were infected with only one virus, whatever this virus was (pH1N1 or NIRVs). Although intense co-circulation of NIRVs (especially hRV) likely brought pH1N1 under the detection threshold, it did not prevent spread of the pandemic Influenza virus within the susceptible population nor induction of an extensive herd immunity to it.

Conclusion

Our results suggest that NIRV co-infections during Influenza epidemics may act as cofactors that contribute to shape an outbreak and modulate the attack rate. They further warrant broad spectrum studies to fully understand viral epidemics.     

The seroprevalence of pandemic influenza H1N1 (2009) virus in China

Background

Mainland China experienced pandemic influenza H1N1 (2009) virus (pH1N1) with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.

Methodology/Principal Findings

Stored serum samples (n = 2,379) collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI) assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40) was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%). Among unvaccinated participants, those aged 6-15 years (32.9%) and 16-24 years (30.3%) had higher seroprevalence compared with participants aged 25–59 years (10.7%) and ≥60 years (9.9%, P<0.0001). Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively). We estimated that 207.7 million individuals (15.9%) experienced pH1N1 infection in China.

Conclusions/Significance

The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.     

Seroprevalence of pandemic (H1N1) 2009 in pregnant women in China: an observational study

Background

We investigated the seropositive rates and persistence of antibody against pandemic (H1N1) 2009 virus (pH1N1) in pregnant women and voluntary blood donors after the second wave of the pandemic in Nanjing, China.

Methodology/Principal Findings

Serum samples of unvaccinated pregnant women (n = 720) and voluntary blood donors (n = 320) were collected after the second wave of 2009 pandemic in Nanjing. All samples were tested against pH1N1 strain (A/California/7/2009) with hemagglutination inhibition assay. A significant decline in seropositive rates, from above 50% to about 20%, was observed in pregnant women and voluntary blood donors fifteen weeks after the second wave of the pandemic. A quarter of the samples were tested against a seasonal H1N1 strain (A/Brisbane/59/2007). The antibody titers against pH1N1 strain were found to correlate positively with those against seasonal H1N1 strain. The correlation was modest but statistically significant.

Conclusions and Significance

The high seropositive rates in both pregnant women and voluntary blood donors suggested that the pH1N1 virus had widely spread in these two populations. Immunity derived from natural infection seemed not to be persistent well.     

Avian influenza H5N1 transmission in households, Indonesia

Background

Disease transmission patterns are needed to inform public health interventions, but remain largely unknown for avian influenza H5N1 virus infections. A recent study on the 139 outbreaks detected in Indonesia between 2005 and 2009 found that the type of exposure to sources of H5N1 virus for both the index case and their household members impacted the risk of additional cases in the household. This study describes the disease transmission patterns in those outbreak households.

Methodology/Principal Findings

We compared cases (n = 177) and contacts (n = 496) in the 113 sporadic and 26 cluster outbreaks detected between July 2005 and July 2009 to estimate attack rates and disease intervals. We used final size household models to fit transmission parameters to data on household size, cases and blood-related household contacts to assess the relative contribution of zoonotic and human-to-human transmission of the virus, as well as the reproduction number for human virus transmission. The overall household attack rate was 18.3% and secondary attack rate was 5.5%. Secondary attack rate remained stable as household size increased. The mean interval between onset of subsequent cases in outbreaks was 5.6 days. The transmission model found that human transmission was very rare, with a reproduction number between 0.1 and 0.25, and the upper confidence bounds below 0.4. Transmission model fit was best when the denominator population was restricted to blood-related household contacts of index cases.

Conclusions/Significance

The study only found strong support for human transmission of the virus when a single large cluster was included in the transmission model. The reproduction number was well below the threshold for sustained transmission. This study provides baseline information on the transmission dynamics for the current zoonotic virus and can be used to detect and define signatures of a virus with increasing capacity for human-to-human transmission.     

H1N1pdm influenza infection in hospitalized cancer patients: clinical evolution and viral analysis

Background

The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil.

Methods

We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir.

Results

A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples.

Conclusions

Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.     

Knowledge,Attitudes, Practices and Emotional Reactions among Residents of Avian Influenza (H5N1) Hit Communities in Vietnam

Background

Awareness of individuals’ knowledge and predicting their behavior and emotional reactions is crucial when evaluating clinical preparedness for influenza pandemics with a highly pathogenic virus. Knowledge, attitude, and practice (KAP) relating to avian influenza (H5N1) virus infection among residents in communities where H5N1 patients occurred in Vietnam has not been reported.

Methods and Principal Findings

Face-to-face interviews including KAP survey were conducted in Bac Kan province, located in the northeast mountainous region of Vietnam. Participants were residents who lived in a community where H5N1 cases have ever been reported (event group, n = 322) or one where cases have not been reported (non-event group, n = 221). Data on emotional reactions of participants and healthcare-seeking behavior after the event in neighboring areas were collected as well as information on demographics and environmental measures, information sources, and KAP regarding H5N1. These data were compared between two groups. Higher environmental risk of H5N1 and improper poultry-handling behaviors were identified in the event group. At the time of the event, over 50% of the event group sought healthcare for flu-like symptoms or because they were scared. Awareness of the event influenced KAP scores. Healthcare-seeking behavior and attention to H5N1 poultry outbreaks diminished in the event group as time passed after the outbreak compared with the non-event group. Factors that motivated participants to seek healthcare sooner were knowledge of early access to healthcare and the risk of eating sick/dead poultry, and perception of the threat of H5N1.

Conclusions

Awareness of H5N1 patients in neighboring areas can provoke panic in residents and influence their healthcare-seeking behavior. Periodic education to share experiences on the occurrence of H5N1 patients and provide accurate information may help prevent panic and infection and reduce mortality. Local conditions should be taken into account when emphasizing the need for early access to healthcare.     

Influenza A (H1N1) in Victoria, Australia: a community case series and analysis of household transmission

Background

We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009.

Methods

Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.

Results

The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms.

Conclusion

Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households.     

Secondary attack rate of tuberculosis in urban households in Kampala, Uganda

Background

Tuberculosis is an ancient disease that continues to threaten individual and public health today, especially in sub-Saharan Africa. Current surveillance systems describe general risk of tuberculosis in a population but do not characterize the risk to an individual following exposure to an infectious case.

Methods

In a study of household contacts of infectious tuberculosis cases (n = 1918) and a community survey of tuberculosis infection (N = 1179) in Kampala, Uganda, we estimated the secondary attack rate for tuberculosis disease and tuberculosis infection. The ratio of these rates is the likelihood of progressive primary disease after recent household infection.

Results

The secondary attack rate for tuberculosis disease was 3.0% (95% confidence interval: 2.2, 3.8). The overall secondary attack rate for tuberculosis infection was 47.4 (95% confidence interval: 44.3, 50.6) and did not vary widely with age, HIV status or BCG vaccination. The risk for progressive primary disease was highest among the young or HIV infected and was reduced by BCG vaccination.

Conclusions

Early case detection and treatment may limit household transmission of M. tuberculosis. Household members at high risk for disease should be protected through vaccination or treatment of latent tuberculosis infection.     

Cluster of Nipah virus infection, Kushtia District, Bangladesh, 2007

Objective

In March 2007, we investigated a cluster of Nipah encephalitis to identify risk factors for Nipah infection in Bangladesh.

Methods

We defined confirmed Nipah cases by the presence of IgM and IgG antibodies against Nipah virus in serum. Case-patients, who resided in the same village during the outbreak period but died before serum could be collected, were classified as probable cases.

Results

We identified three confirmed and five probable Nipah cases. There was a single index case. Five of the secondary cases came in close physical contact to the index case when she was ill. Case-patients were more likely to have physical contact with the index case (71% cases versus 0% controls, p = <0.001). The index case, on her third day of illness, and all the subsequent cases attended the same religious gathering. For three probable cases including the index case, we could not identify any known risk factors for Nipah infection such as physical contact with Nipah case-patients, consumption of raw date palm juice, or contact with sick animals or fruit bats.

Conclusion

Though person-to-person transmission remains an important mode of transmission for Nipah infection, we could not confirm the source of infection for three of the probable Nipah case-patients. Continued surveillance and outbreak investigations will help better understand the transmission of Nipah virus and develop preventive strategies.     

Outbreak of Hepatitis B Virus Infections Associated with Assisted Monitoring of Blood Glucose in an Assisted Living Facility–Virginia, 2010

Introduction

In January 2010, the Virginia Department of Health received reports of 2 hepatitis B virus (HBV) infections (1 acute, 1 chronic) among residents of a single assisted living facility (ALF). Both infected residents had diabetes and received assisted monitoring of blood glucose (AMBG) at the facility. An investigation was initiated in response.

Objective

To determine the extent and mechanism of HBV transmission among ALF residents.

Design

Retrospective cohort study.

Setting

An ALF that primarily housed residents with neuropsychiatric disorders in 2 adjacent buildings in Virginia.

Participants

Residents of the facility as of March 2010.

Measurements

HBV serologic testing, relevant medical history, and HBV genome sequences. Risk ratios (RR) and 95% confidence intervals (CIs) were used to identify risk factors for HBV infection.

Results

HBV serologic status was determined for 126 (91%) of 139 residents. Among 88 susceptible residents, 14 became acutely infected (attack rate, 16%), and 74 remained uninfected. Acute HBV infection developed among 12 (92%) of 13 residents who received AMBG, compared with 2 (3%) of 75 residents who did not (RR  = 35; 95% CI, 8.7, 137). Identified infection control breaches during AMBG included shared use of fingerstick devices for multiple residents. HBV genome sequencing demonstrated 2 building-specific phylogenetic infection clusters, each having 99.8–100% sequence identity.

Limitations

Transfer of residents out of the facility prior to our investigation might have contributed to an underestimate of cases. Resident interviews provided insufficient information to fully assess behavioral risk factors for HBV infection.

Conclusions

Failure to adhere to safe practices during AMBG resulted in a large HBV outbreak. Protection of a growing and vulnerable ALF population requires improved training of staff and routine facility licensing inspections that scrutinize infection control practices.     

Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

Background

Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany.

Methods

Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily.

Results

We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03). Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics. On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status.

Conclusion

Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was limited.     

Factors affecting intention to receive and self-reported receipt of 2009 pandemic (H1N1) vaccine in Hong Kong: a longitudinal study

Background

Vaccination was a core component for mitigating the 2009 influenza pandemic (pH1N1). However, a vaccination program''s efficacy largely depends on population compliance. We examined general population decision-making for pH1N1 vaccination using a modified Theory of Planned Behaviour (TBP).

Methodology

We conducted a longitudinal study, collecting data before and after the introduction of pH1N1 vaccine in Hong Kong. Structural equation modeling (SEM) tested if a modified TPB had explanatory utility for vaccine uptake among adults.

Principal Findings

Among 896 subjects who completed both the baseline and the follow-up surveys, 7% (67/896) reported being “likely/very likely/certain” to be vaccinated (intent) but two months later only 0.8% (7/896) reported having received pH1N1 vaccination. Perception of low risk from pH1N1 (60%) and concerns regarding adverse effects of the vaccine (37%) were primary justifications for avoiding pH1N1 vaccination. Greater perceived vaccine benefits (β = 0.15), less concerns regarding vaccine side-effects (β = −0.20), greater adherence to social norms of vaccination (β = 0.39), anticipated higher regret if not vaccinated (β = 0.47), perceived higher self-efficacy for vaccination (β = 0.12) and history of seasonal influenza vaccination (β = 0.12) were associated with higher intention to receive the pH1N1 vaccine, which in turn predicted self-reported vaccination uptake (β = 0.30). Social norm (β = 0.70), anticipated regret (β = 0.19) and vaccination intention (β = 0.31) were positively associated with, and accounted for 70% of variance in vaccination planning, which, in turn subsequently predicted self-reported vaccination uptake (β = 0.36) accounting for 36% of variance in reported vaccination behaviour.

Conclusions/Significance

Perceived low risk from pH1N1 and perceived high risk from pH1N1 vaccine inhibited pH1N1 vaccine uptake. Both the TPB and the additional components contributed to intended vaccination uptake but social norms and anticipated regret predominantly associated with vaccination intention and planning. Vaccination planning is a more significant proximal determinant of uptake of pH1N1 vaccine than is intention. Intention alone is an unreliable predictor of future vaccine uptake.     

Serologic survey of the pandemic H1N1 2009 virus in Guangdong Province, China: a cross sectional study

Background

Relying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, which urges a deep insight into the serological evidence of infection and transmission feature of pandemic H1N1 2009 (pH1N1) virus in Guangdong province.

Methods

In this cross-sectional serological survey, serum samples were collected by multi-stage stratified random sampling in Jan 2010. Antibody titers were measured by hemagglutination inhibition (HI) assay. Age-specific and region-specific prevalence were calculated based on the results of HI assay (positive, HI titer≥1∶40).

Results

A total of 4,319 serum samples had been collected from subjects without vaccination with pH1N1 vaccine. The seroprevalence was 22.82% (985/4,319). By contrast, there was a marked spatial heterogeneity in prevalence. The seroprevalence was 27.3% in large city, 21.4% in medium cities, higher than that of 20.2% in rural areas. The seroprevalence was highest in 11–20 age group (32.8%), however, in those above 60 years of age group, which was 12.6%, lower than other age groups. On the other hand, antibody titers to pH1N1 virus were highest in school children, which were followed by a gradual decrease in adult. However, in the elderly groups from cities, especially from large city, the antibody titer to pH1N1 increased significantly and reached a much higher level.

Conclusion

Our results showed that the prevalence for pH1N1 was correlated with age and population density. Preexisting antibody may have protected the very old from pH1N1 infection, while original antigenic sin and immunosenescence may have contributed to greater severity once infected. These should be considered when studying the pathogenesis and transmission of influenza virus and formulating strategies on vaccination and treatment.     

Predicting the lay preventive strategies in response to avian influenza from perceptions of the threat

Background

The identification of patterns of behaviors that lay people would engage in to protect themselves from the risk of infection in the case of avian influenza outbreak, as well as the lay perceptions of the threat that underlie these risk reduction strategies.

Methodology/Principal Findings

A population-based survey (N = 1003) was conducted in 2008 to understand and describe how the French public might respond to a possible outbreak. Factor analyses highlighted three main categories of risk reduction strategies consisting of food quality assurance, food avoidance, and animal avoidance. In combination with the fear of contracting avian influenza, mental representations associated with the manifestation and/or transmission of the disease were found to significantly and systematically shape the behavioral responses to the perceived threat.

Conclusions/Significance

This survey provides insight into the nature and predictors of the protective patterns that might be expected from the general public during a novel domestic outbreak of avian influenza.     

Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

Background

The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

Methods

During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.

Results

In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03).

Conclusion

The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.     

Prevalence of 2009 pandemic influenza A (H1N1) virus antibodies, Tampa Bay Florida--November-December, 2009

Background

In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic.

Methods

During November-December 2009, we collected leftover serum from a blood bank, a pediatric children''s hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination.

Results

During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5–17 years (53%) and young adults aged 18–24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11–13%) of pH1N1 virus infection.

Conclusions

After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults.     

Effect of Genital Herpes on Cervicovaginal HIV Shedding in Women Co-Infected with HIV AND HSV-2 in Tanzania

Objectives

To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.

Design

Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined.

Results

Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log₁₀ copies/mL) was closely associated with HIV PVL (β = 0.51 per log₁₀ copies/ml increase, 95%CI:0.41–0.60, p<0.001) and HSV shedding (β = 0.24 per log₁₀ copies/ml increase, 95% CI:0.16–0.32, p<0.001) but not the presence of herpetic lesions (β = −0.10, 95%CI:−0.28–0.08, p = 0.27).

Conclusions

HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility.