Godfrey Musuka

Estimated HIV Trends and Program Effects in Botswana

Background This study uses surveillance, survey and program data to estimate past trends and current levels of HIV in Botswana and the effects of treatment and prevention programs. Methods/Principal Findings Data from sentinel surveillance at antenatal clinics and a national population survey were used to estimate the trend of adult HIV prevalence from 1980 to 2007. Using the prevalence trend we estimated the number of new adult infections, the transmission from mothers to children, the need for treatment and the effects of antiretroviral therapy (ART) and adult and child deaths. Prevalence has declined slowly in urban areas since 2000 and has remained stable in rural areas. National prevalence is estimated at 26% (25–27%) in 2007. About 330,000 (318,000–335,000) people are infected with HIV including 20,000 children. The number of new adult infections has been stable for several years at about 20,000 annually (12,000–26,000). The number of new child infections has declined from 4600 in 1999 to about 890 (810–980) today due to nearly complete coverage of an effective program to prevent mother-to-child transmission (PMTCT). The annual number of adult deaths has declined from a peak of over 15,500 in 2003 to under 7400 (5000–11,000) today due to coverage of ART that reaches over 80% in need. The need for ART will increase by 60% by 2016. Conclusions Botswanas PMTCT and treatment programs have achieved significant results in preventing new child infections and deaths among adults and children. The number of new adult infections continues at a high level. More effective prevention efforts are urgently needed.

Modeling dynamic interactions between pre-exposure prophylaxis interventions & treatment programs: predicting HIV transmission & resistance

Clinical trials have recently demonstrated the effectiveness of Pre-Exposure Prophylaxis (PrEP) in preventing HIV infection. Consequently, PrEP may soon be used for epidemic control. We model the dynamic interactions that will occur between treatment programs and potential PrEP interventions in resource-constrained countries. We determine the consequences for HIV transmission and drug resistance. We use response hypersurface modeling to predict the effect of PrEP on decreasing transmission as a function of effectiveness, adherence and coverage. We predict PrEP will increase need for second-line therapies (SLT) for treatment-naïve individuals, but could significantly decrease need for SLT for treatment-experienced individuals. If the rollout of PrEP is carefully planned it could increase the sustainability of treatment programs. If not, need for SLT could increase and the sustainability of treatment programs could be compromised. Our results show the optimal strategy for rolling out PrEP in resource-constrained countries is to begin around the “worst” treatment programs.

Outcomes of the Botswana national HIV/AIDS treatment programme from 2002 to 2010: a longitudinal analysis

BACKGROUND Short-term mortality rates among patients with HIV receiving antiretroviral therapy (ART) in sub-Saharan Africa are higher than those recorded in high-income countries, but systematic long-term comparisons have not been made because of the scarcity of available data. We analysed the effect of the implementation of Botswanas national ART programme, known as Masa, from 2002 to 2010. METHODS The Masa programme started on Jan 21, 2002. Patients who were eligible for ART according to national guidelines had their data collected prospectively through a clinical information system developed by the Botswana Ministry of Health. A dataset of all available electronic records for adults (≥18 years) who had enrolled by April 30, 2010, was extracted and sent to the study team. All data were anonymised before analysis. The primary outcome was mortality. To assess the effect of loss to follow-up, we did a series of sensitivity analyses assuming varying proportions of the population lost to follow-up to be dead. FINDINGS We analysed the records of 126,263 patients, of whom 102,713 had documented initiation of ART. Median follow-up time was 35 months (IQR 14-56), with a median of eight follow-up visits (4-14). 15,270 patients were deemed lost to follow-up by the end of the study. 63% (78,866) of the study population were women; median age at baseline was 34 years for women (IQR 29-41) and 38 years for men (33-45). 10,230 (8%) deaths were documented during the 9 years of the study. Mortality was highest during the first 3 months after treatment initiation at 12·8 deaths per 100 person-years (95% CI 12·4-13·2), but decreased to 1·16 deaths per 100 person-years (1·12-1·2) in the second year of treatment, and to 0·15 deaths per 100 person-years (0·09-0·25) over the next 7 years of follow-up. In each calendar year after the start of the Masa programme in 2002, average CD4 cell counts at enrolment increased (from 101 cells/μL [IQR 44-156] in 2002, to 191 cells/μL [115-239] in 2010). In each year, the proportion of the total enrolled population who died in that year decreased, from 63% (88 of 140) in 2002, to 0·8% (13 of 1599) in 2010. A sensitivity analysis assuming that 60% of the population lost to follow-up had died gave 3000 additional deaths, increasing overall mortality from 8% to 11-13%. INTERPRETATION The Botswana national HIV/AIDS treatment programme reduced mortality among adults with HIV to levels much the same as in other low-income or middle-income countries. FUNDING The African Comprehensive HIV/AIDS Partnerships.

Assessing the effects of homosexuals and bisexuals on the intrinsic dynamics of HIV/AIDS in heterosexual settings

A deterministic compartmental sex-structured HIV/AIDS model for assessing the effects of homosexuals and bisexuals on the intrinsic dynamics of the disease in heterosexual settings in which homosexuality and bisexuality issues have remained taboo is presented. The epidemic threshold and equilibria for the model are determined and stabilities are investigated. Comprehensive qualitative analysis of the model including invariance of solutions and permanence are carried out. The epidemic threshold known as the basic reproductive number suggests that heterosexuality, homosexuality, and bisexuality influence the growth of the epidemic in HIV/AIDS affected populations and the partial reproductive number (homosexuality induced or heterosexuality and bisexuality induced) with the larger value influences the overall dynamics of the epidemic in a setting. Numerical simulations of the model show that as long as one of the partial reproductive numbers is greater than unity, the disease will exist in the population. We conclude from the study that homosexuality and bisexuality enlarge the epidemic in a heterosexual setting. The theoretical study highlights the need to carry out substantial research to map homosexuals and bisexuals as it has remained unclear as to what extent this group has contributed to the epidemic in heterosexual settings especially in southern Africa, which has remained the epidemiological locus of the epidemic.

HIV/AIDS MODEL ASSESSING THE EFFECTS OF GENDER-INEQUALITY AFFECTING WOMEN IN AFRICAN HETEROSEXUAL SETTINGS

A sex-structured model for heterosexual transmission of HIV/AIDS for addressing the epidemic as a gender-based issue in African heterosexual settings is presented. The epidemic threshold and equilibria for the model are determined and stabilities are investigated. Comprehensive qualitative analysis of the model including positivity and boundedness of solutions, as well as persistence are carried out. The epidemic threshold for the model is computed and used to assess the effects of gender-inequality affecting women in heterosexual settings. The obtained gender-inequality-induced reproductive number R(0) is greater than the reproductive number in the absence of gender-inequality R(0)(*) (R(0) > R(0)(*)) suggesting that gender-inequality affecting women in heterosexual settings enlarges the HIV/AIDS epidemic. Numerical simulations are carried out using demographic and epidemiological parameters for Zimbabwe and the obtained results confirm that gender-inequality increases HIV/AIDS prevalence in heterosexual settings. We conclude from the study that gender-inequality affecting women among heterosexuals should be properly addressed for the effective control of the HIV/AIDS epidemic.

The occurrence of Culicoides species, the vectors of arboviruses, at selected trap sites in Zimbabwe

Abstract A study of the distribution of Culicoides species was conducted by establishing 12 light trap sites over five rainy seasons between 1998 and 2003 covering all the geo-climatic natural regions of Zimbabwe. In total, 279 919 specimens of Culicoides were trapped over a total of 163 trapping nights. The highest median counts of Culicoides per trapping night were recorded in natural region III, which has climatic conditions conducive to the successful development of the larvae. Culicoides imicola, the major vector of bluetongue and African horse sickness viruses in Africa, was found to be the most abundant species (80.4%), followed by Culicoides enderleini (5.9%) and Culicoides milnei (5.2%). This study identified 10 species of Culicoides that had not been previously described in Zimbabwe, including Culicoides loxodontis and Culicoides miombo, which are members of the C. imicola complex. A total of 23 994 Culicoides midges were collected from five trap sites in Harare, Zimbabwe, with the dominant species, C. imicola, representing 91.6% of the total collection. Seventeen arboviruses were isolated from these midges, 15 of which were bluetongue virus. The predominant bluetongue virus serotype was serotype 11, followed by serotypes 1, 8, 12 and 15. Bluetongue virus serotypes 1, 2, 8, 10, 12, 15, 16 and 18, detected in this study, had not been previously reported in Zimbabwe.A study of the distribution of Culicoides species was conducted by establishing 12 light trap sites over five rainy seasons between 1998 and 2003 covering all the geo-climatic natural regions of Zimbabwe. In total, 279 919 specimens of Culicoides were trapped over a total of 163 trapping nights. The highest median counts of Culicoides per trapping night were recorded in natural region III, which has climatic conditions conducive to the successful development of the larvae. Culicoides imicola, the major vector of bluetongue and African horse sickness viruses in Africa, was found to be the most abundant species (80.4%), followed by Culicoides enderleini (5.9%) and Culicoides milnei (5.2%). This study identified 10 species of Culicoides that had not been previously described in Zimbabwe, including Culicoides loxodontis and Culicoides miombo, which are members of the C. imicola complex. A total of 23 994 Culicoides midges were collected from five trap sites in Harare, Zimbabwe, with the dominant species, C. imicola, representing 91.6% of the total collection. Seventeen arboviruses were isolated from these midges, 15 of which were bluetongue virus. The predominant bluetongue virus serotype was serotype 11, followed by serotypes 1, 8, 12 and 15. Bluetongue virus serotypes 1, 2, 8, 10, 12, 15, 16 and 18, detected in this study, had not been previously reported in Zimbabwe.

The sero-prevalence and sero-incidence of African horse sickness and equine encephalosis in selected horse and donkey populations in Zimbabwe

Sentinel herds and samples submitted by private equine practitioners were used to determine the sero-prevalence and sero-incidence of African horse sickness virus (AHSV) and equine encephalosis virus (EEV) in horse and donkey populations in the Highveld region of Zimbabwe. The sero-prevalence and sero-incidence of antibodies against these viruses were determined using the competitive enzyme-linked immunosorbent assay (ELISA) for the detection of serum antibodies. In donkeys, the median sero-prevalence of AHSV antibodies, across the three rainy seasons under study, was 75% (inter quartile range [IQR] 67–83), with a seasonal median sero-incidence of 45% (IQR 40–63). In horses, the median sero-prevalence of EEV antibodies was 63% (IQR 21–73), with a median seasonal sero-incidence of 10.5% (IQR 10–14), while in donkeys the median sero-prevalence of EEV antibodies was 80% (IQR 67–90), with a median seasonal sero-incidence of 50% (IQR 40–60). This study highlighted the significant levels of exposure of donkeys to AHSV and horses and donkeys to EEV in Zimbabwe despite equine encephalosis remaining unreported by Zimbabwean veterinarians to date. Most seroconversions in sentinel herd animals to AHSV and EEV occurred towards the end of the rainy season in March, April and May corresponding to the time of the year when the Culicoides vectors are in high abundance. In order to determine the clinical significance of these infections, blood and spleen samples, submitted by private equine veterinary practitioners over a 5-year period, from horses showing characteristic clinical signs of African horse sickness were tested for the presence of viral antigen using the antigen capture ELISA. The median sero-prevalence of AHSV antigen in horses recorded from these samples was 38% (IQR 33–88). The predominant AHSV antigen from these samples was serotype 7 (33%) followed by serotype 2 (26%) and serotypes 4 and 8 (16% each). African horse sickness virus serotypes 3 and 9, identified in this study, had not been previously reported in Zimbabwe.

The Madikwe Forum: a comprehensive partnership for supporting governance of Botswana's HIV and AIDS response.

There is a need for actors within the philanthropic sector to pursue collaborative partnerships with developing nations which could result in sustainable country-led responses to HIV and AIDS. There is also a need to evaluate the structures governing these partnerships in order to determine their effectiveness in strengthening national responses to HIV and AIDS. This article presents findings from a qualitative study of a governance structure of the African Comprehensive HIV/AIDS Partnerships (ACHAP), namely the Madikwe Forum. The investigation sought to critically reflect on the role and effectiveness of the Madikwe Forum in Botswanas response to HIV and AIDS and to consider the value of such a forum for other developing nations and partnership arrangements. The findings indicate that the Madikwe Forum has enabled considerable progress in the implementation of ACHAP-supported initiatives in Botswana. The constructive working relationship and close alignment between ACHAP and the Botswana governments objectives and priority areas were viewed as critical to this success. However, problems exist regarding the operation of the forum as well as a lack of focus on monitoring and evaluation, which requires the forums urgent attention.

Community attitudes on tuberculosis in Botswana: an opportunity for improving the National Tuberculosis Programme outcomes, 2011

ObjectivesThe Botswana tuberculosis HIV Knowledge Attitude and Practice study sought to assess knowledge, attitudes and practices of communities on TB and identify sources of their information on this disease and HIV. Specific objectives of the study were to: (a) collect baseline information on the knowledge, attitudes, and practices about tuberculosis treatment seeking and adherence behaviors in Botswana. (b) Identify barriers which discourage people who may have smear positive tuberculosis from testing and getting treatment (e.g. social stigma) and constraints which prevent them from initiating and completing treatment.ResultsApproximately 92% of respondents (n = 2029), reported that having TB was not something embarrassing, while about 97% (n = 2030) were not ashamed of having a family member with TB. Approximately 95% (n = 2030) expressed willingness to accommodate their relatives with TB at their homes or, work with TB patients (n = 2026). About 21% of the respondents however, believed in myths that TB infection is a result of either having sex with women who had miscarried (n = 2028), or food poisoning (n = 2031) while about 17% believed that TB infection is a result of sleeping with a widow or widower (n = 2031).

A serosurvey of bluetongue and epizootic haemorrhagic disease in a convenience sample of sheep and cattle herds in Zimbabwe

A convenience sample of sheep and cattle herds around the cities of Harare, Kwekwe and Bulawayo, located in the Highveld region of Zimbabwe, was used to estimate the sero-prevalence and sero-incidence of bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) antibodies. A competitive enzyme-linked immunosorbent assay was used to identify serum antibodies against BTV and EHDV across three rainy seasons. The median sero-prevalence of BTV and EHDV antibodies in cattle was 62% (interquartile range [IQR]: 30–89) and 56% (IQR: 5–77), respectively. In sheep, the median sero-prevalence of BTV and EHDV was 41% (IQR: 19–63) and 0% (IQR: 0–21), respectively. Median sero-incidences of BTV and EHDV antibodies in cattle of 43% (IQR: 22–67) and 27% (IQR: 9–57) respectively were recorded. The median sero-incidence of BTV in sheep was 14% (IQR: 6–23). Based on these preliminary findings, animal health workers in Zimbabwe should continue to monitor the exposure rates of cattle and sheep to BTV and consider the possibility of strains emerging with increased pathogenicity. There are no previous published reports of antibodies against EHDV in Zimbabwe so the possibility of epizootic haemorrhagic disease existing in domestic livestock should now be considered by Zimbabwean animal health officials. Seroconversions to BTV and EHDV occurred predominantly at the end of each rainy season (March and April), which generally corresponds to high numbers of the Culicoides vectors. BTV isolations were made from three individual cows in two of the sentinel herds and all three were identified as serotype 3. This is the first time BTV serotype 3 has been recorded in Zimbabwe, although its presence in neighbouring South Africa is well documented.