Fitting the HIV Epidemic in Zambia: A Two-Sex Micro-Simulation Model

BACKGROUND: In describing and understanding how the HIV epidemic spreads in African countries, previous studies have not taken into account the detailed periods at risk. This study is based on a micro-simulation model (individual-based) of the spread of the HIV epidemic in the population of Zambia, where women tend to marry early and where divorces are not frequent. The main target of the model was to fit the HIV seroprevalence profiles by age and sex observed at the Demographic and Health Survey conducted in 2001. METHODS AND FINDINGS: A two-sex micro-simulation model of HIV transmission was developed. Particular attention was paid to precise age-specific estimates of exposure to risk through the modelling of the formation and dissolution of relationships: marriage (stable union), casual partnership, and commercial sex. HIV transmission was exclusively heterosexual for adults or vertical (mother-to-child) for children. Three stages of HIV infection were taken into account. All parameters were derived from empirical population-based data. Results show that basic parameters could not explain the dynamics of the HIV epidemic in Zambia. In order to fit the age and sex patterns, several assumptions were made: differential susceptibility of young women to HIV infection, differential susceptibility or larger number of encounters for male clients of commercial sex workers, and higher transmission rate. The model allowed to quantify the role of each type of relationship in HIV transmission, the proportion of infections occurring at each stage of disease progression, and the net reproduction rate of the epidemic (R(0) = 1.95). CONCLUSIONS: The simulation model reproduced the dynamics of the HIV epidemic in Zambia, and fitted the age and sex pattern of HIV seroprevalence in 2001. The same model could be used to measure the effect of changing behaviour in the future

Genital Herpes Has Played a More Important Role than Any Other Sexually Transmitted Infection in Driving HIV Prevalence in Africa

Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships

Risk estimates of recurrent congenital anomalies in the UK: a population-based register study

BACKGROUND: Recurrence risks for familial congenital anomalies in successive pregnancies are known, but this information for major structural anomalies is lacking. We estimated the absolute and relative risks of recurrent congenital anomaly in the second pregnancy for women with a history of a congenital anomaly in the first pregnancy; for all major anomaly groups and subtypes. METHODS: Population-based register data on 18,605 singleton pregnancies affected by major congenital anomaly occurring in 872,493 singleton stillbirths, live births and terminations of pregnancy for fetal anomaly were obtained from the Northern Congenital Abnormality Survey, North of England, UK, for 1985-2010. Absolute risks (ARs) and relative risks (RRs) for recurrent congenital anomaly (overall, from a similar group, from a dissimilar group) in the second pregnancy were estimated by history of congenital anomaly (overall, by group, by subtype) in the first pregnancy. RESULTS: The estimated prevalences of congenital anomaly in first and second pregnancies were 276 (95% CI 270-281) and 163 (95% CI 159-168) per 10,000 respectively. For women whose first pregnancy was affected by congenital anomaly, the AR of recurrent congenital anomaly in the second pregnancy was 408 (95% CI 365-456) per 10,000; 2.5 (95% CI 2.3-2.8, p<0.0001) times higher than for those with unaffected first pregnancies. For similar anomalies, the recurrence risk was considerably elevated (RR=23.8, 95% CI 19.6-27.9, P<0.0001) while for dissimilar anomalies the increase was more modest (RR=1.4, 95% CI 1.2-1.6, P=0.001), although the ARs for both were 2%. CONCLUSIONS: Absolute recurrence risks varied between 1 in 20 and 1 in 30 for most major anomaly groups. At pre-conception and antenatal counselling, women whose first pregnancy was affected by a congenital anomaly and who are planning a further pregnancy may find it reassuring that despite high relative risks, the absolute recurrence risk is relatively low

Impact of mass distribution of free long-lasting insecticidal nets on childhood malaria morbidity: The Togo National Integrated Child Health Campaign

<p>Abstract</p> <p>Background</p> <p>An evaluation of the short-term impact on childhood malaria morbidity of mass distribution of free long-lasting insecticidal nets (LLINs) to households with children aged 9-59 months as part of the Togo National Integrated Child Health Campaign.</p> <p>Methods</p> <p>The prevalence of anaemia and malaria in children aged zero to 59 months was measured during two cross-sectional household cluster-sample surveys conducted during the peak malaria transmission, three months before (Sept 2004, n = 2521) and nine months after the campaign (Sept 2005, n = 2813) in three districts representative of Togo's three epidemiological malaria transmission regions: southern tropical coastal plains (Yoto), central fertile highlands (Ogou) and northern semi-arid savannah (Tone).</p> <p>Results</p> <p>In households with children <5 years of age, insecticide-treated net (ITN) ownership increased from <1% to >65% in all 3 districts. Reported ITN use by children during the previous night was 35.9%, 43.8% and 80.6% in Yoto, Ogou and Tone, respectively. Rainfall patterns were comparable in both years. The overall prevalence of moderate to severe anaemia (Hb < 8.0 g/dL) was reduced by 28% (prevalence ratio [PR] 0.72, 95% CI 0.62-0.84) and mean haemoglobin was increased by 0.35 g/dL (95% CI 0.25-0.45).</p> <p>The effect was predominantly seen in children aged 18-59 months and in the two southern districts: PR (95% CI) for moderate to severe anaemia and clinical malaria: Yoto 0.62 (0.44-0.88) and 0.49 (0.35-0.75); Ogou 0.54 (0.37-0.79) and 0.85 (0.57-1.27), respectively. Similar reductions occurred in children <18 months in Ogou, but not in Yoto. No effect was seen in the semi-arid northern district despite a high malaria burden and ITN coverage.</p> <p>Conclusions</p> <p>A marked reduction in childhood malaria associated morbidity was observed in the year following mass distribution of free LLINs in two of the three districts in Togo. Sub-national level impact evaluations will contribute to a better understanding of the impact of expanding national malaria control efforts.</p

Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach

Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence

High Prevalence of Malaria in Zambezia, Mozambique: The Protective Effect of IRS versus Increased Risks Due to Pig-Keeping and House Construction

BACKGROUND: African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed. METHODS: Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1-15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed. RESULTS: Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%-57.1%) in children 1-15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%-27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%-77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR)= 0.6; 95%CI: 0.4-0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3-0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5-0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0-1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1-4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3-2.4) versus other roofing materials and bigger household size (8-15 people: OR = 1.6; 95%CI: 1.3-2.1) versus small households (1-4 persons). CONCLUSION: Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs