Rudzani Muloiwa

Associations between asthma and bronchial hyper-responsiveness with allergy and atopy phenotypes in urban black South African teenagers

OBJECTIVES To determine asthma and allergy phenotypes in unselected urban black teenagers and to associate bronchial hyper-responsiveness (BHR) with asthma, other atopic diseases and allergen sensitisation. METHODS This was a cross-sectional study of 211 urban high-school black children of Xhosa ethnicity. Modified ISAAC questionnaires regarding asthma, eczema and rhinitis were administered. BHR was assessed by methacholine challenge using hand-held nebulisers. Skinprick tests (SPTs) were performed for 8 aeroallergens and 4 food allergens. RESULTS Asthma was reported in 9%, and 16 % demonstrated BHR. Rhinitis was reported in 48% and eczema in 19%. Asthma was strongly associated with BHR. Asthma was associated with eczema whereas BHR was associated with rhinitis. SPTs were positive in 34% of subjects, aeroallergens in 32%, and food allergens in 5%. The most common sensitivities were to house dust mites (HDM) and German cockroach. BHR was associated with sensitivity to any aeroallergen, cat, HDM, cockroach and bermuda grass. The number of positive SPTs was associated with asthma and BHR. With each level of SPT positivity, there was 40% increased prevalence of asthma and 70% increased prevalence of BHR. The rate of allergen sensitisation in subjects with BHR (72%) was much higher than those without BHR (28%); house dust mite sensitivity was 69% in subjects with BHR and 18% in those without. CONCLUSIONS These are the highest rates of allergen sensitisation in subjects with BHR documented in an African setting and the widest difference in sensitisation rates between subjects with and without BHR.

Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

The incidence of cutaneous adverse drug reactions (CADRs) to first‐line antituberculosis drugs (FLTDs) is higher in HIV–tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied.

Incidence and Diagnosis of Pertussis in South African Children Hospitalized With Lower Respiratory Tract Infection.

Background: The incidence of pertussis in children in low- and middle-income countries is poorly described. This study aimed to prospectively investigate the incidence of pertussis in South African children hospitalized with lower respiratory tract infection (LRTI). Methods: Children hospitalized with LRTI in Cape Town, South Africa were enrolled over 1 year. Clinical data were collected. A nasopharyngeal (NP) swab and induced sputum (IS) were taken, and polymerase chain reaction specific for Bordetella pertussis (IS481+/hIS1001−) and Bordetella parapertussis (IS1001+) was performed. Results: A total of 460 children with median age 8 [interquartile range (IQR), 4–18] months were studied. B. pertussis was detected in 17 (3.7%) while total Bordetella spp. were identified on 23 (5.0 %) of 460 NP. Adding IS testing increased the identification of B. pertussis to 32 of 460 cases (7.0%; 95% confidence interval, 4.8%–9.7%); P = 0.028 and total Bordetella to 41 of 460 (8.9%; 95% confidence interval, 4–10%); P = 0.020. Shorter duration of symptoms [median 2 (IQR, 2–3) days versus 5 (IQR, 3–7) days; P = 0.0008] was associated with detection of B. pertussis on IS versus NP. B. pertussis was detected in 15.8% (n=3/19) of HIV-infected children, 10.9% (n = 10/92) of HIV exposed uninfected and 5.4% (n = 19/349) of HIV-unexposed uninfected children. Risk of B. pertussis decreased with each additional dose of diphtheria, tetanus and acellular pertussis vaccine [0 doses = 17.9%; 1 dose = 7.0%; 2 doses = 6.9%; and >3 doses = 6.2%]. Conclusions: Pertussis is common in South African children hospitalized with LRTI particularly if HIV exposed or infected but decreases sequentially with vaccination doses. Polymerase chain reaction on IS specimen provides confirmation earlier than NP while increasing overall diagnostic yield.

The burden of pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunization (EPI) in 1974: a systematic review protocol.

BackgroundVaccine against pertussis has been in use for several decades. Despite the widespread use of pertussis vaccine, evidence shows resurgence of pertussis in high-income countries. Pertussis surveillance data is largely missing from low- and middle-income countries (LMICs). Without data on trends of pertussis, it is difficult to review and amend pertussis control policies in any country. We propose conducting a systematic review to evaluate the burden and trends of pertussis in LMICs since 1974.Methods/designCommon and medical subject heading (MeSH) terms for pertussis and LMICs will be used to search electronic databases for the relevant literature published between 1974 and December 2014. Only studies from LMICs that fulfils World Health Organisation (WHO) or CDC pertussis case definitions will be included. The studies must have a clear numerator and denominator in a well-defined population.Risk of bias will be evaluated by assessing all qualifying full-text articles for quality and eligibility using a modified quality score assessment tool.Standardised data extraction will be carried out after which descriptions of trends in the prevalence, incidence, as well as mortality rate and case fatality rate, will be done. Where sufficient data is available, the results will be stratified by age group, geography, location, vaccination and HIV status.DiscussionThe systematic review proposed by this protocol seeks to address the knowledge gap in the epidemiology of pertussis in LMICs for the first time. It is anticipated that the background epidemiological trends of pertussis in LMICs that our study will provide could be used in the planning for the control of pertussis.Systematic review registrationPROSPERO CRD42015015159

Factors associated with increased mortality in a predominantly HIV-infected population with Stevens Johnson syndrome and toxic epidermal necrolysis.

Introduction Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug reactions with a higher incidence in HIV-infected persons. SJS/TEN are associated with skin and mucosal failure, predisposing to systemic bacterial infection (BSI), a major cause of death. There are limited data on risk factors associated with BSI and and mortality in HIV-infected people with SJS/TEN. Methods We conducted a retrospective study of patients admitted to a university hospital with SJS/TEN over a 3 year period. We evaluated their underlying illnesses, eliciting drugs, predictive value of bacterial skin cultures and other factors associated with mortality and BSI in a predominantly HIV-infected population by comparing characteristics of the patients who demised and those who survived. Results We admitted 86 cases during the study period and 67/86(78%) were HIV-infected. Tuberculosis was the commonest co-morbidity, diagnosed in 12/86(14%) cases. Skin cultures correlated with BSI by the same organism in 7/64(11%) cases and 6/7 were Gram-negative. Two of the 8 cases of Gram-negative BSI had an associated Gram-negative skin culture, although not always the same organism. All 8 fatalities had >30% epidermal detachment, 7 were HIV-infected, 6 died of BSI and 6 had tuberculosis. Conclusions Having >30% epidermal detachment in SJS/TEN carries an increased risk of BSI and mortality. Tuberculosis and BSI are associated with higher risk of death in SJS/TEN. Our data suggests there may be an association between Gram-negative BSI and Gram-negative skin infection.

Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women

Introduction Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population. Methods We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes. Results We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73%) had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95%) cases. All 22 of the mothers survived with 3/22 (14%) developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50%) babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine. Conclusions TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS‐KS

Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposis sarcoma (KS). Six major subtypes (A‐F), based on genetic variability of open reading frame (ORF)‐K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF‐K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)‐KS and 5 African endemic‐KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02–9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease. J. Med. Virol. 88:292–303, 2016.

Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases

BACKGROUND Isoniazid and ethionamide are important first- and second-line anti-TB drugs (FLDs and SLDs), respectively. Ethionamide is a structural analogue of isoniazid and the two drugs share other similarities, including their metabolism, therapeutic targets, hepato-toxicity patterns and drug resistance. As a result, there has always been concern about possible cross-reactivity between them. METHODS Among 69 patients with drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) to FLDs, FLDs were stopped and SLDs added when the skin and laboratory parameters had settled. This was followed by sequential and additive rechallenge with FLDs. We report 25 consecutive cases that developed confirmed cutaneous adverse drug reactions (CADRs) to isoniazid or ethionamide used as FLD and SLD, respectively. RESULTS Sixty-nine participants who developed CADRs on FLDs were enrolled in the study. Twenty developed a rechallenge reaction to isoniazid and five reacted to ethionamide. Four of the 20 isoniazid cases were patch test positive, 3/20 were skin prick test positive and 13/20 reacted to oral rechallenge. All seven cases that were patch and skin prick test positive were associated with systemic reactions. Twenty of the 25 cases had DRESS and 5 had SJS/TEN. Twenty-three of the 25 cases with rechallenge reactions were HIV infected. Importantly, none of the cases that reacted to ethionamide during the rechallenge reacted to isoniazid and none who subsequently reacted to isoniazid reacted to ethionamide. CONCLUSIONS Our findings strongly suggest that the risk of cross-reactivity of isoniazid and ethionamide in DRESS syndrome and SJS/TEN is low. These findings have implications for clinical management.

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. Trial registration number CRD42015026144.

Race trouble: experiences of Black medical specialist trainees in South Africa

BackgroundThis research aimed to identify and explore the experiences of Black registrars in their training in the Western Cape’s academic hospitals in order to identify structures, practices, attitudes and ideologies that may promote or impede the advancement of Black doctors into specialist medicine. This is justified by the requirement for universities to work towards monitoring and evaluating efforts to create non-discriminatory and inclusive training environments.MethodsThis study employed qualitative research methods. Ten Black African medical specialists were interviewed about their training experiences in two university training hospitals in the Western Cape Province, South Africa. Interview data was collected using open-ended questions and coded and analysed using thematic and critical discursive analysis techniques.ResultsFour experiential themes emerged from the interview data, they included: 1) experiences of everyday racism during work hours, 2) the physical and psychological effects of tokenism and an increased need to perform, 3) institutional racism as a result of inconsistent and unclear methods of promotion and clinical competence building, and 4) an organisational culture that was experienced as having a race and gender bias.ConclusionThis is a pilot study and there are limits on the generalizability of the data due to the small sample. What is clear from our participants, though, is the strong experiential component of finding it challenging to be a Black trainee in a White-dominated profession. We are undertaking further research to explore the issues raised in more detail.