Individual- and Household-Level Risk Factors Associated with Malaria in Mutasa District, Zimbabwe: A Serial Cross-Sectional Study.

Malaria constitutes a major public health problem in Zimbabwe, particularly in the north and east bordering Zambia and Mozambique. In Manicaland Province in eastern Zimbabwe, malaria transmission is seasonal and unstable. Over the past decade, Manicaland Province has reported increased malaria transmission due to limited funding, drug resistance and insecticide resistance. The aim of this study was to identify risk factors at the individual and household levels to better understand the epidemiology of malaria and guide malaria control strategies in eastern Zimbabwe. Between October 2012 and September 2014, individual demographic data and household characteristics were collected from cross-sectional surveys of 1,116 individuals residing in 316 households in Mutasa District, one of the worst affected districts. Factors associated with malaria, measured by rapid diagnostic test (RDT), were identified through multilevel logistic regression models. A total of 74 participants were RDT positive. Sleeping under a bed net had a protective effect against malaria despite pyrethroid resistance in the mosquito vector. Multivariate analysis showed that malaria risk was higher among individuals younger than 25 years, residing in households located at a lower household density and in closer proximity to the Mozambique border. The risk factors identified need to be considered in targeting malaria control interventions to reduce host-vector interactions.

High-Resolution Plasmodium falciparum Malaria Risk Mapping in Mutasa District, Zimbabwe: Implications for Regaining Control.

In Zimbabwe, more than half of malaria cases are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. The objectives of this study were to develop a prediction model based on environmental risk factors and obtain seasonal malaria risk maps for Mutasa District, one of the worst affected districts in Manicaland Province. From October 2012 to September 2015, 483 households were surveyed, and 104 individuals residing within 69 households had positive rapid diagnostic test results. Logistic regression was used to model the probability of household positivity as a function of the environmental covariates extracted from high-resolution remote sensing data sources. Model predictions and prediction standard errors were generated for the rainy and dry seasons. The resulting maps predicted elevated risk during the rainy season, particularly in low-lying areas bordering Mozambique. In contrast, the risk of malaria was low across the study area during the dry season with foci of malaria risk scattered along the northern and western peripheries of the study area. These findings underscore the need for strong cross-border malaria control initiatives to complement country-specific interventions.

Reduction in Malaria Incidence following Indoor Residual Spraying with Actellic 300 CS in a Setting with Pyrethroid Resistance: Mutasa District, Zimbabwe.

BACKGROUND: More than half of malaria cases in Zimbabwe are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. Recently, high levels of pyrethroid and carbamate resistance were detected in Anopheles funestus, the major malaria vector in eastern Zimbabwe. In response, a single round of indoor residual spraying (IRS) using pirimiphos-methyl (an organophosphate) was implemented in four high burden districts of Manicaland Province from November 1, 2014 to December 19, 2014. The objective of this study was to evaluate the effect of this programmatic switch in insecticides on malaria morbidity reported from health care facilities in Mutasa District, one of the worst affected districts in Manicaland Province. METHODS: The number of weekly malaria cases for each health facility 24 months prior to the 2014 IRS campaign and in the subsequent high transmission season were obtained from passive case surveillance. Environmental variables were extracted from remote-sensing data sources and linked to each health care facility. Negative binomial regression was used to model the weekly number of malaria cases, adjusted for seasonality and environmental variables. RESULTS: From December 2012 to May 2015, 124,206 malaria cases were reported from 42 health care facilities in Mutasa District. Based on a higher burden of malaria, 20 out of 31 municipal wards were sprayed in the district. Overall, 87.3% of target structures were sprayed and 92.1% of the target population protected. During the 6 months after the 2014 IRS campaign, a period when transmission would have otherwise peaked, the incidence of malaria was 38% lower than the preceding 24 months at health facilities in the sprayed wards. CONCLUSIONS: Pirimiphos-methyl had a measurable impact on malaria incidence and is an effective insecticide for the control of An. funestus in eastern Zimbabwe.

Increasing adolescent HIV prevalence in Eastern Zimbabwe--evidence of long-term survivors of mother-to-child transmission?

Recent data from the Manicaland HIV/STD Prevention Project, a general-population open HIV cohort study, suggested that between 2004 and 2007 HIV prevalence amongst males aged 15-17 years in eastern Zimbabwe increased from 1.20% to 2.23%, and in females remained unchanged at 2.23% to 2.39%, while prevalence continued to decline in the rest of the adult population. We assess whether the more likely source of the increase in adolescent HIV prevalence is recent sexual HIV acquisition, or the aging of long-term survivors of perinatal HIV acquisition that occurred during the early growth of the epidemic. Using data collected between August 2006 and November 2008, we investigated associations between adolescent HIV and (1) maternal orphanhood and maternal HIV status, (2) reported sexual behaviour, and (3) reporting recurring sickness or chronic illness, suggesting infected adolescents might be in a late stage of HIV infection. HIV-infected adolescent males were more likely to be maternal orphans (RR = 2.97, p<0.001) and both HIV-infected adolescent males and females were more likely to be maternal orphans or have an HIV-infected mother (male RR = 1.83, p<0.001; female RR = 16.6, p<0.001). None of 22 HIV-infected adolescent males and only three of 23 HIV-infected females reported ever having had sex. HIV-infected adolescents were 60% more likely to report illness than HIV-infected young adults. Taken together, all three hypotheses suggest that recent increases in adolescent HIV prevalence in eastern Zimbabwe are more likely attributable to long-term survival of mother-to-child transmission rather than increases in risky sexual behaviour. HIV prevalence in adolescents and young adults cannot be used as a surrogate for recent HIV incidence, and health systems should prepare for increasing numbers of long-term infected adolescents.

Changes in the burden of malaria following scale up of malaria control interventions in Mutasa District, Zimbabwe.

BACKGROUND: To better understand trends in the burden of malaria and their temporal relationship to control activities, a survey was conducted to assess reported cases of malaria and malaria control activities in Mutasa District, Zimbabwe. METHODS: Data on reported malaria cases were abstracted from available records at all three district hospitals, three rural hospitals and 25 rural health clinics in Mutasa District from 2003 to 2011. RESULTS: Malaria control interventions were scaled up through the support of the Roll Back Malaria Partnership, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and The President's Malaria Initiative. The recommended first-line treatment regimen changed from chloroquine or a combination of chloroquine plus sulphadoxine/pyrimethamine to artemisinin-based combination therapy, the latter adopted by 70%, 95% and 100% of health clinics by 2008, 2009 and 2010, respectively. Diagnostic capacity improved, with rapid diagnostic tests (RDTs) available in all health clinics by 2008. Vector control consisted of indoor residual spraying and distribution of long-lasting insecticidal nets. The number of reported malaria cases initially increased from levels in 2003 to a peak in 2008 but then declined 39% from 2008 to 2010. The proportion of suspected cases of malaria in older children and adults remained high, ranging from 75% to 80%. From 2008 to 2010, the number of RDT positive cases of malaria decreased 35% but the decrease was greater for children younger than five years of age (60%) compared to older children and adults (26%). CONCLUSIONS: The burden of malaria in Mutasa District decreased following the scale up of malaria control interventions. However, the persistent high number of cases in older children and adults highlights the need for strategies to identify locally effective control measures that target all age groups.

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009.

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.

Challenges and prospects for malaria elimination in the Southern Africa region.

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, including regions of Southern Africa. Important to effective regional malaria control in Southern Africa is the appreciation that the reductions in malaria have not been achieved uniformly, with some countries experiencing resurgence. Understanding the reasons for sustained low-level malaria transmission in the face of control efforts, why malaria control efforts have not been successful in particular epidemiological settings and the epidemiological and transmission patterns following resurgence are critical to improving further malaria control and possible elimination. The overall goal of the International Center of Excellence for Malaria Research in Southern Africa is to contribute to regional malaria control efforts that can be sustained beyond the duration of the project. This goal will be achieved through a combination of: (1) state-of-the-art research on malaria epidemiology, vector biology and the genetics of the malaria parasite in three different epidemiological settings; (2) collaborations with national malaria control programs to develop locally adapted and sustainable control strategies; and (3) training, career development and capacity building at research institutions throughout the region.

Malaria epidemiology and control in Southern Africa.

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, following the scale-up of interventions supported by the Roll Back Malaria Partnership, the President's Malaria Initiative and other partners. It is important to appreciate that the reductions in malaria have not been uniform between and within countries, with some areas experiencing resurgence instead. Furthermore, while interventions have greatly reduced the burden of malaria in many countries, it is also recognized that the malaria decline pre-dated widespread intervention efforts, at least in some cases where data are available. This raises more questions as what other factors may have been contributing to the reduction in malaria transmission and to what extent. The International Center of Excellence for Malaria Research (ICEMR) in Southern Africa aims to better understand the underlying malaria epidemiology, vector ecology and parasite genomics using three contrasting settings of malaria transmission in Zambia and Zimbabwe: an area of successful malaria control, an area of resurgent malaria and an area where interventions have not been effective. The Southern Africa ICEMR will capitalize on the opportunity to investigate the complexities of malaria transmission while adapting to intervention and establish the evidence-base to guide effective and sustainable malaria intervention strategies. Key approaches to attain this goal for the region will include close collaboration with national malaria control programs and contribution to capacity building at the individual, institutional and national levels.

Potential impact of reactive vaccination in controlling cholera outbreaks: an exploratory analysis using a Zimbabwean experience.

BACKGROUND: To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. OBJECTIVES: To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent large-scale cholera outbreak in Zimbabwe. METHODS: This was a retrospective cost-effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-adjusted life year (DALY) averted. RESULTS: Under the base-case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1 320 deaths and 23 650 DALYs. Considering herd immunity, the corresponding values would have been 2 920 deaths and 52 360 DALYs averted. The total vaccination costs would have been ~$74 million and ~$21 million, respectively, with per-dose vaccine price of US$5 and $1. The incremental costs per DALY averted of reactive vaccination were $2 770 and $370, respectively, for vaccine price set at $5 and $1. Assuming herd immunity, the corresponding cost was $980 with vaccine price of $5, and the programme was cost-saving with a vaccine price of $1. Results were most sensitive to case-fatality rate, per-dose vaccine price, and the size of the outbreak. CONCLUSIONS: Reactive vaccination has the potential to be a cost-effective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-depth studies.

Descriptive spatial analysis of the cholera epidemic 2008-2009 in Harare, Zimbabwe: a secondary data analysis.

This ecological study describes the cholera epidemic in Harare during 2008-2009 and identifies patterns that may explain transmission. Rates ratios of cholera cases by suburb were calculated by a univariate regression Poisson model and then, through an Empirical Bayes modelling, smoothed rate ratios were estimated and represented geographically. Mbare and southwest suburbs of Harare presented higher rate ratios. Suburbs attack rates ranged from 1.2 (95% Cl = 0.7-1.6) cases per 1000 people in Tynwald to 90.3 (95% Cl = 82.8-98.2) in Hopley. The identification of this spatial pattern in the spread, characterised by low risk in low density residential housing, and a higher risk in high density south west suburbs and Mbare, could be used to advocate for improving water and sanitation conditions and specific preparedness measures in the most affected areas.

Measuring and correcting biased child mortality statistics in countries with generalized epidemics of HIV infection.

OBJECTIVE: Under Millennium Development Goal 4, countries are required to reduce child mortality by two-thirds between 1990 and 2015. In countries with generalized epidemics of human immunodeficiency virus (HIV) infection, standard statistics based on fertility history may misrepresent progress towards this target owing to the correlation between deaths among mothers and early childhood deaths from acquired immunodeficiency syndrome. METHODS: To empirically estimate this bias, child mortality data and fertility history, including births to deceased women, were collected through prospective household surveys in eastern Zimbabwe during 1998-2005. A mathematical model was then used to investigate the determinants and temporal dynamics of the bias, first in Zimbabwe and then in other countries with different background mortality rates and HIV-related epidemic profiles. FINDINGS: According to the empirical data, standard cross-sectional survey statistics underestimated true infant and under-5 mortality by 6.7% and 9.8%, respectively. These estimates were in agreement with the output from the model, in which the bias varied according to the magnitude and stage of the epidemic of HIV infection and background mortality rates. The bias was greater the longer the period elapsed before the survey and in later stages of the epidemic. Bias could substantially distort the measured effect of interventions to reduce non-HIV-related mortality and of programmes to prevent mother-to-child transmission, especially when trends are based on data from a single survey. CONCLUSION: The correlation between the HIV-related deaths of mothers and their children can bias survey estimates of early child mortality. A mathematical model with a user-friendly interface is available to correct for this bias when measuring progress towards Millennium Development Goal 4 in countries with generalized epidemics of HIV infection.

Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe (DETECTB): a cluster-randomised trial.

BACKGROUND: Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission. METHODS: Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥16 years) residents volunteering chronic cough (≥2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452. FINDINGS: 46 study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11-1·96, p=0·0087). The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1-8·3) to 3·7 per 1000 adults (2·6-5·0; adjusted risk ratio 0·59, 95% CI 0·40-0·89, p=0·0112). INTERPRETATION: Wide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease. FUNDING: Wellcome Trust.

The risk and timing of tuberculosis diagnosed in smear-negative TB suspects: a 12 month cohort study in Harare, Zimbabwe.

BACKGROUND: Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges. METHODS AND FINDINGS: Between February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3). HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals. CONCLUSION: We found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay.

Provider-initiated symptom screening for tuberculosis in Zimbabwe: diagnostic value and the effect of HIV status.

OBJECTIVE: To assess the diagnostic value of provider-initiated symptom screening for tuberculosis (TB) and how HIV status affects it. METHODS: We performed a secondary analysis of randomly selected participants in a community-based TB-HIV prevalence survey in Harare, Zimbabwe. All completed a five-symptom questionnaire and underwent sputum TB culture and HIV testing. We calculated the sensitivity, specificity, and positive and negative predictive values of various symptoms and used regression analysis to investigate the relationship between symptoms and TB disease. FINDINGS: We found one or more symptoms of TB in 21.2% of 1858 HIV-positive (HIV+) and 9.9% of 7121 HIV-negative (HIV-) participants (P < 0.001). TB was subsequently diagnosed in 48 HIV+ and 31 HIV- participants. TB was asymptomatic in 18 culture-positive individuals, 8 of whom (4 in each HIV status group) had positive sputum smears. Cough of any duration, weight loss and, for HIV+ participants only, drenching night sweats were independent predictors of TB. In HIV+ participants, cough of > or = 2 weeks' duration, any symptom and a positive sputum culture had sensitivities of 48%, 81% and 65%, respectively; in HIV- participants, the sensitivities were 45%, 71% and 74%, respectively. Symptoms had a similar sensitivity and specificity in HIV+ and HIV- participants, but in HIV+ participants they had a higher positive and a lower negative predictive value. CONCLUSION: Even smear-positive TB may be missed by provider-initiated symptom screening, especially in HIV+ individuals. Symptom screening is useful for ruling out TB, but better TB diagnostics are urgently needed for resource-poor settings.

Identifying recent Mycobacterium tuberculosis transmission in the setting of high HIV and TB burden.

BACKGROUND: Accurate diagnosis of latent tuberculosis infection (LTBI) in recently exposed HIV-infected tuberculosis (TB) contacts is a public health priority because of the high risk of progression to active TB but is hampered by the high background prevalence of LTBI in high-burden populations and poor sensitivity of tuberculin skin testing (TST) in HIV co-infection. METHODS: The prevalence of LTBI in 222 recent household contacts of TB cases and 176 household contacts of community controls without TB in Harare, Zimbabwe were compared using TST and interferon gamma enzyme-linked immunospot (ELISpot) responses to ESAT-6 (early secretory antigenic target-6) and CFP-10 (culture filtrate protein-10). TST and ELISpot results were correlated with markers of recent TB exposure and the impact of HIV co-infection was assessed. RESULTS: In this high-incidence population, the proportion of ELISpot-positive contacts was not significantly different from community controls. However, ELISpot, unlike TST, revealed a higher prevalence of LTBI in recent contacts of sputum smear-positive cases than in contacts of controls. ELISpot results correlated significantly with positive sputum smear and culture status of the index case (adjusted OR 2.40, CI 1.12 to 5.14), even in the subgroup of HIV-infected contacts (adjusted OR 5.36, CI 1.11 to 25.93). and were independent of contacts' HIV status. TST results were also associated with positive smear and culture status of the index case (adjusted OR 4.41, CI 1.82 to 10.67) but were negatively associated with contacts' HIV status (adjusted OR 0.25, CI 0.10 to 0.60). CONCLUSIONS: Contact investigations in high-burden populations should focus on contacts of sputum smear-positive cases in whom recent infection can be detected by ELISpot, even in the presence of HIV co-infection.

Zimbabwe experiences the worst epidemic of cholera in Africa.

A severe outbreak of cholera has been reported in Zimbabwe since mid 2008, with so far over 92,000 cases and over 4,000 deaths. This outbreak has differed from previous outbreaks in being mainly urban and with a high case-fatality rate. Breakdown in the supply of clean water has been the main underlying cause but breakdown in health service delivery in Zimbabwe has also contributed to the magnitude and severity of the outbreak.

Female genital schistosomiasis--a differential diagnosis to sexually transmitted disease: genital itch and vaginal discharge as indicators of genital Schistosoma haematobium morbidity in a cross-sectional study in endemic rural Zimbabwe.

OBJECTIVE: To examine the association between schistosomiasis and reproductive tract symptoms. METHOD: A cross-sectional study was conducted in a Schistosoma haematobium-endemic area of rural Zimbabwe. A total of 483 permanently resident adult women of Mupfure Ward aged 20-49 were interviewed and examined clinically, each providing three consecutive urine samples. Logistic regression analysis was used to control for sexually transmitted diseases (STDs). RESULTS: Women with genital sandy patches had significantly more genital itch (P = 0.009) and perceived their discharge as abnormal (P = 0.003). Eighty percent of the women who had genital itch, yellow discharge, and childhood or current waterbody contact had sandy patches. Fifty-two percent of the women with genital sandy patches did not have detectable S. haematobium ova in urine. Genital schistosomiasis was associated with stress incontinence and pollakisuria, but not with menstrual irregularities, current or previous ulcers, or tumours. CONCLUSION: Genital schistosomiasis may be a differential diagnosis to the STDs in women who have been exposed to fresh water in endemic areas. Because of the chronic nature of the disease in adults, we suggest to pay special attention to the prevention of morbidity.