Big Baby, Little Mother: Tsetse Flies Are Exceptions to the Juvenile Small Size Principle.

While across the animal kingdom offspring are born smaller than their parents, notable exceptions exist. Several dipteran species belonging to the Hippoboscoidea superfamily can produce offspring larger than themselves. In this essay, the blood-feeding tsetse is focused on. It is suggested that the extreme reproductive strategy of this fly is enabled by feeding solely on highly nutritious blood, and producing larval offspring that are soft and malleable. This immense reproductive expenditure may have evolved to avoid competition with other biting flies. Tsetse also transmit blood-borne parasites that cause the fatal diseases called African trypanosomiases. It is discussed how tsetse life history and reproductive strategy profoundly influence the type of vector control interventions used to reduce fly populations. In closing, it is argued that the unusual life history of tsetse warrants their preservation in the areas where human and animal health is not threatened.

Does Counting Different Life Stages Impact Estimates for Extinction Probabilities for Tsetse (Glossina spp)?

As insect populations decline, due to climate change and other environmental disruptions, there has been an increased interest in understanding extinction probabilities. Generally, the life cycle of insects occurs in well-defined stages: when counting insects, questions naturally arise about which life stage to count. Using tsetse flies (vectors of trypanosomiasis) as a case study, we develop a model that works when different life stages are counted. Previous branching process models for tsetse populations only explicitly represent newly emerged adult female tsetse and use that subpopulation to keep track of population growth/decline. Here, we directly model other life stages. We analyse reproduction numbers and extinction probabilities and show that several previous models used for estimating extinction probabilities for tsetse populations are special cases of the current model. We confirm that the reproduction number is the same regardless of which life stage is counted, and show how the extinction probability depends on which life stage we start from. We demonstrate, and provide a biological explanation for, a simple relationship between extinction probabilities for the different life stages, based on the probability of recruitment between stages. These results offer insights into insect population dynamics and provide tools that will help with more detailed models of tsetse populations. Population dynamics studies of insects should be clear about life stages and counting points.

Climate change and African trypanosomiasis vector populations in Zimbabwe's Zambezi Valley: A mathematical modelling study.

BACKGROUND: Quantifying the effects of climate change on the entomological and epidemiological components of vector-borne diseases is an essential part of climate change research, but evidence for such effects remains scant, and predictions rely largely on extrapolation of statistical correlations. We aimed to develop a mechanistic model to test whether recent increases in temperature in the Mana Pools National Park of the Zambezi Valley of Zimbabwe could account for the simultaneous decline of tsetse flies, the vectors of human and animal trypanosomiasis. METHODS AND FINDINGS: The model we developed incorporates the effects of temperature on mortality, larviposition, and emergence rates and is fitted to a 27-year time series of tsetse caught from cattle. These catches declined from an average of c. 50 flies per animal per afternoon in 1990 to c. 0.1 in 2017. Since 1975, mean daily temperatures have risen by c. 0.9°C and temperatures in the hottest month of November by c. 2°C. Although our model provided a good fit to the data, it cannot predict whether or when extinction will occur. CONCLUSIONS: The model suggests that the increase in temperature may explain the observed collapse in tsetse abundance and provides a first step in linking temperature to trypanosomiasis risk. If the effect at Mana Pools extends across the whole of the Zambezi Valley, then transmission of trypanosomes is likely to have been greatly reduced in this warm low-lying region. Conversely, rising temperatures may have made some higher, cooler, parts of Zimbabwe more suitable for tsetse and led to the emergence of new disease foci.

Modelling the use of insecticide-treated cattle to control tsetse and Trypanosoma brucei rhodesiense in a multi-host population.

We present a mathematical model for the transmission of Trypanosoma brucei rhodesiense by tsetse vectors to a multi-host population. To control tsetse and T. b. rhodesiense, a proportion, ψ, of cattle (one of the hosts considered in the model) is taken to be kept on treatment with insecticides. Analytical expressions are obtained for the basic reproduction number, R0n in the absence, and R(0n)(T) in the presence of insecticide-treated cattle (ITC). Stability analysis of the disease-free equilibrium was carried out for the case when there is one vertebrate host untreated with insecticide. By considering three vertebrate hosts (cattle, humans and wildlife) the sensitivity analysis was carried out on the basic reproduction number (R(0n)(T)) in the absence and presence of ITC. The results show that R(03)(T) is more sensitive to changes in the tsetse mortality. The model is then used to study the control of tsetse and T. b. rhodesiense in humans through application insecticides to cattle either over the whole-body or to restricted areas of the body known to be favoured tsetse feeding sites. Numerical results show that while both ITC strategies result in decreases in tsetse density and in the incidence of T. b. rhodesiense in humans, the restricted application technique results in improved cost-effectiveness, providing a cheap, safe, environmentally friendly and farmer based strategy for the control of vectors and T. b. rhodesiense in humans.

Modelled impact of Tiny Targets on the distribution and abundance of riverine tsetse.

BACKGROUND: The insecticide-treated baits known as Tiny Targets are one of the cheapest means of controlling riverine species of tsetse flies, the vectors of the trypanosomes that cause sleeping sickness in humans. Models of the efficacy of these targets deployed near rivers are potentially useful in planning control campaigns and highlighting the principles involved. METHODS AND PRINCIPAL FINDINGS: To evaluate the potential of models, we produced a simple non-seasonal model of the births, deaths, mobility and aging of tsetse, and we programmed it to simulate the impact of seven years of target use against the tsetse, Glossina fuscipes fuscipes, in the riverine habitats of NW Uganda. Particular attention was given to demonstrating that the model could explain three matters of interest: (i) good control can be achieved despite the degradation of targets, (ii) local elimination of tsetse is impossible if invasion sources are not tackled, and (iii) with invasion and target degradation it is difficult to detect any effect of control on the age structure of the tsetse population. CONCLUSIONS: Despite its simplifications, the model can assist planning and teaching, but allowance should be made for any complications due to seasonality and management challenges associated with greater scale.

Identification of the area sampled by traps: A modelling study with tsetse.

BACKGROUND: Sampling with traps provides the most common means of investigating the abundance, composition and condition of tsetse populations. It is thus important to know the size of the area from which the samples originate, but that topic is poorly understood. METHODS AND PRINCIPAL FINDINGS: The topic was clarified with the aid of a simple deterministic model of the mobility, births and deaths of tsetse. The model assessed how the sampled area changed according to variations in the numbers, arrangement and catching efficiency of traps deployed for different periods in a large block of homogeneous habitat subject to different levels of fly mortality. The greatest impacts on the size of the sampled area are produced by the flies' mean daily step length and the duration of trapping. There is little effect of trap type. The daily death rate of adult flies is unimportant unless tsetse control measures increase the mortality several times above the low natural rates. CONCLUSIONS: Formulae for predicting the probability that any given captured fly originated from various areas around the trap are produced. Using a mean daily step length (d) of 395m, typical of a savannah species of tsetse, any fly caught by a single trap in a 5-day trapping period could be regarded, with roughly 95% confidence, as originating from within a distance of 1.3km of the trap that is from an area of 5.3km2.

Negative density-dependent dispersal in tsetse (Glossina spp): An artefact of inappropriate analysis.

Published analysis of genetic material from field-collected tsetse (Glossina spp, primarily from the Palpalis group) has been used to predict that the distance (δ) dispersed per generation increases as effective population densities (De) decrease, displaying negative density-dependent dispersal (NDDD). Using the published data we show this result is an artefact arising primarily from errors in estimates of S, the area occupied by a subpopulation, and thereby in De. The errors arise from the assumption that S can be estimated as the area ([Formula: see text]) regarded as being covered by traps. We use modelling to show that such errors result in anomalously high correlations between [Formula: see text] and [Formula: see text] and the appearance of NDDD, with a slope of -0.5 for the regressions of log([Formula: see text]) on log([Formula: see text]), even in simulations where we specifically assume density-independent dispersal (DID). A complementary mathematical analysis confirms our findings. Modelling of field results shows, similarly, that the false signal of NDDD can be produced by varying trap deployment patterns. Errors in the estimates of δ in the published analysis were magnified because variation in estimates of S were greater than for all other variables measured, and accounted for the greatest proportion of variation in [Formula: see text]. Errors in census population estimates result from an erroneous understanding of the relationship between trap placement and expected tsetse catch, exacerbated through failure to adjust for variations in trapping intensity, trap performance, and in capture probabilities between geographical situations and between tsetse species. Claims of support in the literature for NDDD are spurious. There is no suggested explanation for how NDDD might have evolved. We reject the NDDD hypothesis and caution that the idea should not be allowed to influence policy on tsetse and trypanosomiasis control.

Extinction probabilities as a function of temperature for populations of tsetse (Glossina spp.).

Significant reductions in populations of tsetse (Glossina spp) in parts of Zimbabwe have been attributed to increases in temperature over recent decades. Sustained increases in temperature might lead to local extinctions of tsetse populations. Extinction probabilities for tsetse populations have not so far been estimated as a function of temperature. We develop a time-homogeneous branching process model for situations where tsetse live at different levels of fixed temperature. We derive a probability distribution pk(T) for the number of female offspring an adult female tsetse is expected to produce in her lifetime, as a function of the fixed temperature at which she is living. We show that pk(T) can be expressed as a geometric series: its generating function is therefore a fractional linear type. We obtain expressions for the extinction probability, reproduction number, time to extinction and growth rates. The results are valid for all tsetse, but detailed effects of temperature will vary between species. No G. m. morsitans population can escape extinction if subjected, for extended periods, to temperatures outside the range 16°C-32°C. Extinction probability increases more rapidly as temperatures approach and exceed the upper and lower limits. If the number of females is large enough, the population can still survive even at high temperatures (28°C-31°C). Small decreases or increases in constant temperature in the neighbourhoods of 16°C and 31°C, respectively, can drive tsetse populations to extinction. Further study is needed to estimate extinction probabilities for tsetse populations in field situations where temperatures vary continuously.

Uncertainty and sensitivity analyses of extinction probabilities suggest that adult female mortality is the weakest link for populations of tsetse (Glossina spp).

BACKGROUND: A relatively simple life history allows us to derive an expression for the extinction probability of populations of tsetse, vectors of African sleeping sickness. We present the uncertainty and sensitivity analysis of the extinction probability, to offer key insights into factors affecting the control or eradication of tsetse populations. METHODS: We represent tsetse population growth as a branching process, and derive closed form estimates of population extinction from that model. Statistical and mathematical techniques are used to analyse the uncertainties in estimating extinction probability, and the sensitivity of the extinction probability to changes in input parameters representing the natural life history and vital dynamics of tsetse populations. RESULTS: For fixed values of input parameters, the sensitivity of extinction probability depends on the baseline parameter values. Extinction probability is most sensitive to the probability that a female is inseminated by a fertile male when daily pupal mortality is low, whereas the extinction probability is most sensitive to daily mortality rate for adult females when daily pupal mortality, and extinction probabilities, are high. Global uncertainty and sensitivity analysis show that daily mortality rate for adult females has the highest impact on the extinction probability. CONCLUSIONS: The high correlation between extinction probability and daily female adult mortality gives a strong argument that control techniques which increase daily female adult mortality may be the single most effective means of ensuring eradication of tsetse population.

Assessing the effect of insecticide-treated cattle on tsetse abundance and trypanosome transmission at the wildlife-livestock interface in Serengeti, Tanzania.

In the absence of national control programmes against Rhodesian human African trypanosomiasis, farmer-led treatment of cattle with pyrethroid-based insecticides may be an effective strategy for foci at the edges of wildlife areas, but there is limited evidence to support this. We combined data on insecticide use by farmers, tsetse abundance and trypanosome prevalence, with mathematical models, to quantify the likely impact of insecticide-treated cattle. Sixteen percent of farmers reported treating cattle with a pyrethroid, and chemical analysis indicated 18% of individual cattle had been treated, in the previous week. Treatment of cattle was estimated to increase daily mortality of tsetse by 5-14%. Trypanosome prevalence in tsetse, predominantly from wildlife areas, was 1.25% for T. brucei s.l. and 0.03% for T. b. rhodesiense. For 750 cattle sampled from 48 herds, 2.3% were PCR positive for T. brucei s.l. and none for T. b. rhodesiense. Using mathematical models, we estimated there was 8-29% increase in mortality of tsetse in farming areas and this increase can explain the relatively low prevalence of T. brucei s.l. in cattle. Farmer-led treatment of cattle with pyrethroids is likely, in part, to be limiting the spill-over of human-infective trypanosomes from wildlife areas.

Tuberculosis reinfection rate as a proportion of total infection rate correlates with the logarithm of the incidence rate: a mathematical model.

In a significant number of instances, an episode of tuberculosis can be attributed to a reinfection event. Because reinfection is more likely in high incidence regions than in regions of low incidence, more tuberculosis (TB) cases due to reinfection could be expected in high-incidence regions than in low-incidence regions. Empirical data from regions with various incidence rates appear to confirm the conjecture that, in fact, the incidence rate due to reinfection only, as a proportion of all cases, correlates with the logarithm of the incidence rate, rather than with the incidence rate itself. A theoretical model that supports this conjecture is presented. A Markov model was used to obtain a relationship between incidence and reinfection rates. It was assumed in this model that the rate of reinfection is a multiple, rho (the reinfection factor), of the rate of first-time infection, lambda. The results obtained show a relationship between the proportion of cases due to reinfection and the rate of incidence that is approximately logarithmic for a range of values of the incidence rate typical of those observed in communities across the globe. A value of rho is determined such that the relationship between the proportion of cases due to reinfection and the logarithm of the incidence rate closely correlates with empirical data. From a purely theoretical investigation, it is shown that a simple relationship can be expected between the logarithm of the incidence rates and the proportions of cases due to reinfection after a prior episode of TB. This relationship is sustained by a rate of reinfection that is higher than the rate of first-time infection and this latter consideration underscores the great importance of monitoring recovered TB cases for repeat disease episodes, especially in regions where TB incidence is high. Awareness of this may assist in attempts to control the epidemic.

Improved estimates for extinction probabilities and times to extinction for populations of tsetse (Glossina spp).

A published study used a stochastic branching process to derive equations for the mean and variance of the probability of, and time to, extinction in population of tsetse flies (Glossina spp) as a function of adult and pupal mortality, and the probabilities that a female is inseminated by a fertile male. The original derivation was partially heuristic and provided no proofs for inductive results. We provide these proofs, together with a more compact way of reaching the same results. We also show that, while the published equations hold good for the case where tsetse produce male and female offspring in equal proportion, a different solution is required for the more general case where the probability (ß) that an offspring is female lies anywhere in the interval (0, 1). We confirm previous results obtained for the special case where ß = 0.5 and show that extinction probability is at a minimum for ß > 0.5 by an amount that increases with increasing adult female mortality. Sensitivity analysis showed that the extinction probability was affected most by changes in adult female mortality, followed by the rate of production of pupae. Because females only produce a single offspring approximately every 10 days, imposing a death rate of greater than about 3.5% per day will ensure the eradication of any tsetse population. These mortality levels can be achieved for some species using insecticide-treated targets or cattle-providing thereby a simple, effective and cost-effective method of controlling and eradicating tsetse, and also human and animal trypanosomiasis. Our results are of further interest in the modern situation where increases in temperature are seeing the real possibility that tsetse will go extinct in some areas, without the need for intervention, but have an increased chance of surviving in other areas where they were previously unsustainable due to low temperatures.

Evaluation of the Performance of Three Biomarker Assays for Recent HIV Infection Using a Well-Characterized HIV-1 Subtype C Incidence Cohort.

Biomarkers for detecting early HIV infection and estimating HIV incidence should minimize false-recent rates (FRRs) while maximizing mean duration of recent infection (MDRI). We compared HIV subtypes B, E and D (BED) capture enzyme immunoassay (BED), Sedia limiting antigen (LAg) avidity enzyme immunoassay, and Bio-Rad avidity incidence (BRAI) assays using samples from Zimbabwean postpartum women infected with clade C HIV. We calculated MDRIs using 590 samples from 351 seroconverting postpartum women, and FRRs using samples from 2,825 women known to be HIV positive for >12 months. Antibody kinetics were more predictable with LAg and had higher precision compared with BED or BRAI. BRAI also exhibited more variability, and avidity reversal in some cases. For BED, LAg, and BRAI, used alone or with viral load, MDRI values in days were: BED-188 and 170 at normalized optical density (ODn) 0.8; LAg-104 and 100 at ODn cutoff 1.5; BRAI-135 and 134 at avidity index cutoff 30%. Corresponding FRRs were: BRAI 1.1% and 1.0% and LAg 0.57% and 0.35%: these were 3.8-10.9 times lower than BED values of 4.8% and 3.8%. BRAI and LAg have significantly lower FRRs and MDRIs than in published studies, and much lower than BED and could be used to estimate incidence in perinatal women and to measure population-level HIV incidence in HIV control operations in Africa.

How maternal investment varies with environmental factors and the age and physiological state of wild tsetse Glossina pallidipes and Glossina morsitans morsitans.

Theory suggests females should optimize resource allocation across reproductive bouts to maximize lifetime reproduction, balancing current and future reproductive efforts according to physiological state and projected survival and reproduction. Tests of these ideas focus on long-lived vertebrates: few measure age-related reproductive output in iteroparous invertebrates, or partition reserves between those allocated to offspring versus mothers. We investigated how maternal age, and environmental and physiological factors influence reproductive investment in wild tsetse, Glossina pallidipes Austen and G. morsitans morsitans Westwood. Tsetse provide a tractable system to measure reproductive allocation. Females exhibit high maternal investment, producing single, large offspring that rely exclusively on maternal reserves. We find that mothers in better physiological condition and experiencing cooler temperatures produce larger offspring. Pupal size increases significantly but weakly with age. In both species, females with less fat invest proportionately more in offspring. Post-partum fat decreases in flies with badly frayed wings: poor flight capability may limit their feeding efficiency, or they may sacrifice more reserves as a terminal investment. Our results support evidence that offspring size increases with maternal size, investment depends on the environment, and females with lower chances of future reproduction invest more into current offspring. We discuss the implications of maternal effects for predicting vector population responses to environmental change.

Geostatistical models using remotely-sensed data predict savanna tsetse decline across the interface between protected and unprotected areas in Serengeti, Tanzania.

Monitoring abundance is essential for vector management, but it is often only possible in a fraction of managed areas. For vector control programmes, sampling to estimate abundance is usually carried out at a local-scale (10s km2), while interventions often extend across 100s km2. Geostatistical models have been used to interpolate between points where data are available, but this still requires costly sampling across the entire area of interest. Instead, we used geostatistical models to predict local-scale spatial variation in the abundance of tsetse-vectors of human and animal African trypanosomes-beyond the spatial extent of data to which models were fitted, in Serengeti, Tanzania.We sampled Glossina swynnertoni and Glossina pallidipes >10 km inside the Serengeti National Park (SNP) and along four transects extending into areas where humans and livestock live. We fitted geostatistical models to data >10 km inside the SNP to produce maps of abundance for the entire region, including unprotected areas.Inside the SNP, the mean number of G. pallidipes caught per trap per day in dense woodland was 166 (± 24 SE), compared to 3 (±1) in grassland. Glossina swynnertoni was more homogenous with respective means of 15 (±3) and 15 (±8). In general, models predicted a decline in abundance from protected to unprotected areas, related to anthropogenic changes to vegetation, which was confirmed during field survey. Synthesis and applications. Our approach allows vector control managers to identify sites predicted to have relatively high tsetse abundance, and therefore to design and implement improved surveillance strategies. In East and Southern Africa, trypanosomiasis is associated with wilderness areas. Our study identified pockets of vegetation which could sustain tsetse populations in farming areas outside the Serengeti National Park. Our method will assist countries in identifying, monitoring and, if necessary, controlling tsetse in trypanosomiasis foci. This has specific application to tsetse, but the approach could also be developed for vectors of other pathogens.

A dynamic model for estimating adult female mortality from ovarian dissection data for the tsetse fly Glossina pallidipes Austen sampled in Zimbabwe.

Human and animal trypanosomiasis, spread by tsetse flies (Glossina spp), is a major public health concern in much of sub-Saharan Africa. The basic reproduction number of vector-borne diseases, such as trypanosomiasis, is a function of vector mortality rate. Robust methods for estimating tsetse mortality are thus of interest for understanding population and disease dynamics and for optimal control. Existing methods for estimating mortality in adult tsetse, from ovarian dissection data, often use invalid assumptions of the existence of a stable age distribution, and age-invariant mortality and capture probability. We develop a dynamic model to estimate tsetse mortality from ovarian dissection data in populations where the age distribution is not necessarily stable. The models correspond to several hypotheses about how temperature affects mortality: no temperature dependence (model 1), identical temperature dependence for mature adults and immature stages, i.e., pupae and newly emerged adults (model 2), and differential temperature dependence for mature adults and immature stages (model 3). We fit our models to ovarian dissection data for G. pallidipes collected at Rekomitjie Research Station in the Zambezi Valley in Zimbabwe. We compare model fits to determine the most probable model, given the data, by calculating the Akaike Information Criterion (AIC) for each model. The model that allows for a differential dependence of temperature on mortality for immature stages and mature adults (model 3) performs significantly better than models 1 and 2. All models produce mortality estimates, for mature adults, of approximately 3% per day for mean daily temperatures below 25°C, consistent with those of mark-recapture studies performed in other settings. For temperatures greater than 25°C, mortality among immature classes of tsetse increases substantially, whereas mortality remains roughly constant for mature adults. As a sensitivity analysis, model 3 was simultaneously fit to both the ovarian dissection and trap data; while this fit also produces comparable mortality at temperatures below 25°C, it is not possible to obtain good fits to both data sources simultaneously, highlighting the uncertain correspondence between trap catches and population levels and/or the need for further improvements to our model. The modelling approach employed here could be applied to any substantial time series of age distribution data.

Host-seeking efficiency can explain population dynamics of the tsetse fly Glossina morsitans morsitans in response to host density decline.

Females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring. For tsetse-vectors of the trypanosomes that cause human and animal African trypanosomiasis-the problem is more extreme, since both sexes feed solely on blood. Host location is thus essential both for survival and reproduction. Host population density should therefore be an important driver of population dynamics for haematophagous insects, and particularly for tsetse, but the role of host density is poorly understood. We investigate the issue using data on changes in numbers of tsetse (Glossina morsitans morsitans Westwood) caught during a host elimination experiment in Zimbabwe in the 1960s. During the experiment, numbers of flies caught declined by 95%. We aimed to assess whether models including starvation-dependent mortality could explain observed changes in tsetse numbers as host density declined. An ordinary differential equation model, including starvation-dependent mortality, captured the initial dynamics of the observed tsetse population. However, whereas small numbers of tsetse were caught throughout the host elimination exercise, the modelled population went extinct. Results of a spatially explicit agent-based model suggest that this discrepancy could be explained by immigration of tsetse into the experimental plot. Variation in host density, as a result of natural and anthropogenic factors, may influence tsetse population dynamics in space and time. This has implications for Trypanosoma brucei rhodesiense transmission. Increased tsetse mortality as a consequence of low host density may decrease trypanosome transmission, but hungrier flies may be more inclined to bite humans, thereby increasing the risk of transmission to humans. Our model provides a way of exploring the role of host density on tsetse population dynamics and could be incorporated into models of trypanosome transmission dynamics to better understand how spatio-temporal variation in host density impacts trypanosome prevalence in mammalian hosts.

Short Communication: Heightened HIV Antibody Responses in Postpartum Women as Exemplified by Recent Infection Assays: Implications for Incidence Estimates.

Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first 9 months, or at later stages, postpartum. At cutoffs (C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI, estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and 52% lower than published estimates of 287, 152 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7%-19% shorter for women who seroconverted in the first 9 months postpartum than for those seroconverting later. MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunological activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states.

Association of genital shedding of herpes simplex virus type 2 and HIV-1 among sex workers in rural Zimbabwe.

INTRODUCTION: Herpes simplex virus type 2 (HSV-2) facilitates sexual acquisition of HIV-1 but data on transmission are less clear. In this study the interaction between genital shedding of HIV-1 and HSV-2 was explored among Zimbabwean sex workers. METHODS: Women (n = 214) were interviewed about genital symptoms. Blood samples were analysed for HIV-1 and HSV-2 antibodies, HIV-1 plasma viral load (PVL) and CD4 lymphocyte count and genital swabs for detection of HIV-1 and HSV-2 genital shedding, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, and a cervico-vaginal lavage (CVL) for quantitative measurement of HIV-1 shedding. Shedding analyses were undertaken on women co-infected with HSV-2 and HIV-1. RESULTS: A total of 124 women were co-infected with HIV-1 and HSV-2; 58 were infected with HSV-2 alone. Most HIV-1-infected women were co-infected with HSV-2 (95.4%). Genital HIV-1 shedding was detected in 84.3% of co-infected women and was associated with low CD4 cell count and high PVL but not with reported symptoms of genital herpes or genital shedding of HSV-2. There was no difference in HIV-1 shedding among women shedding HSV-2 (79.3%) and women not shedding HSV-2 (83.2%) (P = 0.64). The adjusted odds ratio for HIV-1 shedding between HSV-2 shedders and non-shedders was 0.8 [95% confidence interval (CI), 0.2-3.3]. HIV-1 PVL(log10) and CVL viral load(log10) were correlated (r = 0.38; 95%CI, 0.2-0.5). After adjusting for PVL, genital symptoms and age, HSV-2 shedding had no effect on CVL viral load (P = 0.13). CONCLUSION: Rate and quantity of HIV-1 genital shedding do not appear to be altered by presence of HSV-2 genital shedding.

HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation.

OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce incident HIV among post-partum women and identify risk factors for HIV incidence. DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV-negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum, respectively. Vitamin A supplementation had no impact on incidence [hazard ratio (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum retinol was measured, those with levels indicative of deficiency (< 0.7 micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more likely to seroconvert than women with higher concentrations. Furthermore, among women with low serum retinol, vitamin A supplementation tended to be protective against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not significantly so, perhaps due to limited statistical power. Severe anaemia (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater incidence. Younger women were at higher risk of HIV infection: incidence declined by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum women, a single large-dose vitamin A supplementation had no effect on incidence, although low serum retinol was a risk factor for seroconversion. Further investigation is required to determine whether vitamin A supplementation of vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.