High Efficacy of Combined Albendazole and Ivermectin Treatment Against Gastrointestinal Nematodes in Vervet Monkeys and Baboons

Conventional treatment that eliminates other gastrointestinal nematodes has failed to show adequate efficacy against Trichuris trichura in non-human primates (NHPs). We investigated the efficacy of albendazole and ivermectin against natural infestation of nematodes in non human primates. 18 vervet monkeys (Chlorocebus aethiops) and 21 baboons (Papio anubis) were divided into three treatment groups comprising of 6 vervets and 7 baboons per group. Albendazole (ABZ, 7.5mg/kg) was administered orally, and ivermectin (IVM, 300μg/kg) subcutaneously, each for three consecutive days. Group I animals were treated with a combination of albendazole and ivermectin, Group II ABZ alone, while Group III animals were treated with IVM alone. Faecal samples were collected at 0, 7, 14 and 28 days post treatment (dpt) and analysed for the presence of faecal eggs using the McMaster and formol ether acetyl (FEA) methods. Faecal egg count reduction percentage (FECR (%)) and cure rate (CR (%) i.e. percentage of faecal egg negative individuals after treatment) were used to determine the efficacy of the treatment regimens. The FEA method was found to be a more sensitive assessment method than the McMaster technique. When both methods were used the helminths observed included Trichuris trichura (100% in both NHPs) and strongyles (29.4% in vervets and 28.6% in baboons). In vervets, the FECR of T. trichura at 28 dpt was 100% (Group I), 75% (Group II) and 0% (Group III) while the CR (at the same time point) was 100% (Group I), 60% (Group II) and 0% (Group III). In baboons, the FECR% and CR% of T. trichura at 28dpt, for groups I, II, III was 100%, 100%, 0%, respectively. All the three drug regimens were curative (100%) of strongyles at 28 dpt. It is concluded that a combined ivermectin and albendazole treatment for 3 days is effective in treating T. trichura and strongyles infections in vervet monkeys and baboons. Further trials should be conducted using a bigger sample size as well as in other primates including humans

Influence of Cyclophosphamide on the Haematological Profile of Laboratory Bred African Soft-furred Rats (Mastomys natalensis)

The African soft-furred rat (Mastomys natalensis) has been shown to be a possible model for propagation  of Trypanosoma brucei gambiense. This study aimed at determining the baseline biological reference values  and reproductive data of a laboratory bred Mastomys colony, which was established at TRC. In addition,  the effect of cyclophosphamide (an immunosuppressant) treatment (s) on the haematological profile  was investigated. The mean gestation period was 23 days and the mean litter size was eight. At birth, the  pups weighed 2.4±0.23 g and the weights increased to 78.0±10.6 g in males and 53.9±4.5 g in females by  90 days. The mean haematological values were significantly (p<0.05) higher in adults than juveniles.  However, there was no statistical difference of haematological values between the sexes.  Cyclophosphamide treatment caused a macrocytic hypochromic anaemia, which was noted 24 hours after  treatment and was more severe in animals treated more than once. Thus, in studies involving a disease that  causes anaemia, repeated cyclophosphamide treatment should be limited. Our study is a contribution to  the clinical and biological characterization of the disease pattern in this preferred rodent model of T. b.  gambiense.

Prevalence and Types of Coinfections in Sleeping Sickness Patients in Kenya (2000/2009)

The occurrence of coinfections in human African trypanosomiasis (HAT) patients was investigated using a retrospective data of hospital records at the National Sleeping Sickness Referral Hospital in Alupe, Kenya. A total of 31 patients, 19 males and 12 females, were diagnosed with HAT between the years 2000 and 2009. The observed co-infections included malaria (100%), helminthosis (64.5%), typhoid (22.5%), urinary tract infections (16.1%), HIV (12.9%), and tuberculosis (3.2%). The species of helminthes observed included Ancylostoma duodenale (38.7%), Ascaris lumbricoides (45.7%), Strongyloides stercoralis (9.7%), and Taenia spp. (3.2%). The patients were also infected with Entamoeba spp. (32.3%) and Trichomonas hominis (22.6%) protozoan parasites. The main clinical signs observed at the point of admission included headache (74.2%), fever (48.4%), sleep disorders (45.2%), and general body pain (41.9%). The HAT patients were treated with suramin (early stage, 9/31) and melarsoprol (late stage, 22/31). In conclusion, the study has shown that HAT patients have multiple co-infections which may influence the disease pathogenesis and complicate management of HAT

Use of the nested polymerase chain reaction for detection of Toxoplasma gondii in slaughterhouse workers in Thika District, Kenya

Background. The widely used methods of diagnosis of Toxoplasma gondii are serological. Current reports indicate a high seroprevalence of T. gondii in humans in Kenya. There is a need for more sensitive diagnostic tests, especially when the specific antibody titres are below detectable threshold levels. Use of the polymerase chain reaction (PCR) targeting the repetitive 529 base pair loci has been reported to be sensitive and specific.Objective. To detect T. gondii in a high-risk group of public health workers in Thika District, Kenya.Methods. In total, 87 human blood samples were collected from male slaughterhouse workers between 1 March 2013 and 25 June 2013. The DNA extracted was amplified by the nested PCR.Results. T. gondii was detected in 39.1% (34/87) of the workers. In the cow-sheep-goat slaughterhouses the prevalence ranged between 20% and 60%, while all the chicken slaughterhouse workers (6/6, 100%) tested positive. The difference in T. gondii positivity between the workers in the chicken slaughterhouse and those in the cattle-sheep-goat slaughterhouses was statistically significant (p=0.003).Conclusion. This study shows the presence of T. gondii in an asymptomatic high-risk group in Thika District, indicating the need for enhancement of public health awareness

A Fatal Outbreak of Campylobacter jejuni Enteritis in a Colony of Vervet Monkeys in Kenya

In a group of 50 wild-caught vervet monkeys trapped for experimental studies, 23 developed severe diarrhoea  during the quarantine period. While 10 of these responded well to routine treatment with metronidazole,  kaomycin and oral electrolytes, 13 initially showed slight improvement but later relapsed. Five of  these failed to respond altogether and were euthanised. Fresh faecal samples were collected from the surviving  eight monkeys and analysed for microbiology and drug sensitivity. Campylobacter jejuni, sensitive  to erythromycin, was isolated from all the faecal samples. Following treatment with erythromycin, seven  monkeys recovered fully within ten days but one died before the end of therapy. This study indicates that  wild non-human primates may play a significant role as a reservoir of C. jejuni, whereby they may act as  natural carriers of this human pathogen. Screening for Campylobacter sp in newly acquired monkeys is  advisable as part of the quarantine procedures.

First reported case of fatal tuberculosis in a wild African elephant with past human-wildlife contact

Tuberculosis is emerging/re-emerging in captive elephant populations, where it causes morbidity and deaths, although no case of TB in wild African elephants has been reported. In this paper we report the first case of fatal TB in an African elephant in the wild. The infection with Mycobacterium tuberculosis was confirmed by post-mortem and histological examinations of a female sub-adult elephant aged >12 years that died in Tsavo East National Park, Kenya, while under treatment. This case is unique in that during its lifetime the elephant had contact with both humans and wild elephants. The source of the infection was unclear because the elephant could have acquired the infection in the orphanage or in the wild. However, our results show that wild elephants can maintain human TB in the wild and that the infection can be fata

Use of the nested polymerase chain reaction for detection of Toxoplasma gondii in slaughterhouse workers in Thika District, Kenya

Background. The widely used methods of diagnosis of Toxoplasma gondii are serological. Current reports indicate a high seroprevalence of T. gondii in humans in Kenya. There is a need for more sensitive diagnostic tests, especially when the specific antibody titres are below detectable threshold levels. Use of the polymerase chain reaction (PCR) targeting the repetitive 529 base pair loci has been reported to be sensitive and specific.Objective. To detect T. gondii in a high-risk group of public health workers in Thika District, Kenya.Methods. In total, 87 human blood samples were collected from male slaughterhouse workers between  1 March 2013 and  25 June 2013. The DNA extracted was amplified by the nested PCR.Results. T. gondii was detected in 39.1% (34/87) of the workers. In the cow-sheep-goat slaughterhouses the prevalence ranged between 20% and 60%, while all the chicken slaughterhouse workers (6/6, 100%) tested positive. The difference in T. gondii positivity between the workers in the chicken slaughterhouse and those in the cattle-sheep-goat slaughterhouses was statistically significant (p=0.003).Conclusion. This study shows the presence of T. gondiiin an asymptomatic high-risk group in Thika District, indicating the need for enhancement of public health awareness.

Neopterin is a cerebrospinal fluid marker for treatment outcome evaluation in patients affected by Trypanosoma brucei gambiense sleeping sickness.

BACKGROUND: Post-therapeutic follow-up is essential to confirm cure and to detect early treatment failures in patients affected by sleeping sickness (HAT). Current methods, based on finding of parasites in blood and cerebrospinal fluid (CSF) and counting of white blood cells (WBC) in CSF, are imperfect. New markers for treatment outcome evaluation are needed. We hypothesized that alternative CSF markers, able to diagnose the meningo-encephalitic stage of the disease, could also be useful for the evaluation of treatment outcome. METHODOLOGY/PRINCIPAL FINDINGS: Cerebrospinal fluid from patients affected by Trypanosoma brucei gambiense HAT and followed for two years after treatment was investigated. The population comprised stage 2 (S2) patients either cured or experiencing treatment failure during the follow-up. IgM, neopterin, B2MG, MMP-9, ICAM-1, VCAM-1, CXCL10 and CXCL13 were first screened on a small number of HAT patients (n = 97). Neopterin and CXCL13 showed the highest accuracy in discriminating between S2 cured and S2 relapsed patients (AUC 99% and 94%, respectively). When verified on a larger cohort (n = 242), neopterin resulted to be the most efficient predictor of outcome. High levels of this molecule before treatment were already associated with an increased risk of treatment failure. At six months after treatment, neopterin discriminated between cured and relapsed S2 patients with 87% specificity and 92% sensitivity, showing a higher accuracy than white blood cell numbers. CONCLUSIONS/SIGNIFICANCE: In the present study, neopterin was highlighted as a useful marker for the evaluation of the post-therapeutic outcome in patients suffering from sleeping sickness. Detectable levels of this marker in the CSF have the potential to shorten the follow-up for HAT patients to six months after the end of the treatment

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised